Mitochondrial Diseases
Mitochondrial Encephalomyopathies
MELAS Syndrome
DNA, Mitochondrial
MERRF Syndrome
Kearns-Sayre Syndrome
Ophthalmoplegia, Chronic Progressive External
RNA, Transfer, Leu
Diffuse Cerebral Sclerosis of Schilder
Leigh Disease
Genes, Mitochondrial
Cytochrome-c Oxidase Deficiency
Mitochondria
Electron Transport Complex I
Oxidative Phosphorylation
Electron Transport Complex IV
Ubiquinone
Brain Diseases, Metabolic, Inborn
Mitochondria, Muscle
Mutation
Mitochondrial Proteins
Acidosis, Lactic
Exome
Optic Atrophy, Hereditary, Leber
NADH Dehydrogenase
Cell Respiration
Mitochondrial Proton-Translocating ATPases
Point Mutation
Intestinal Pseudo-Obstruction
Dichloroacetic Acid
Phenotype
Electron Transport Complex II
Succinate Dehydrogenase
Polarography
DNA-Directed DNA Polymerase
RNA, Transfer, Lys
Spinocerebellar Degenerations
Ophthalmoplegia
Electron Transport
Metabolism, Inborn Errors
Anemia, Sideroblastic
Succinic Acid
Mitochondrial ADP, ATP Translocases
Muscle, Skeletal
Mutation, Missense
Pedigree
Nervous System Diseases
Molecular Sequence Data
Lactic Acid
Base Sequence
Sequence Analysis, DNA
Fibroblasts
Reactive Oxygen Species
Cardiomyopathies
Brain
Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: implications for mitochondrial DNA replication, expression and disease. (1/884)
The selective manipulation of mitochondrial DNA (mtDNA) replication and expression within mammalian cells has proven difficult. One promising approach is to use peptide nucleic acid (PNA) oligomers, nucleic acid analogues that bind selectively to complementary DNA or RNA sequences inhibiting replication and translation. However, the potential of PNAs is restricted by the difficulties of delivering them to mitochondria within cells. To overcome this problem we conjugated a PNA 11mer to a lipophilic phosphonium cation. Such cations are taken up by mitochondria through the lipid bilayer driven by the membrane potential across the inner membrane. As anticipated, phosphonium-PNA (ph-PNA) conjugates of 3.4-4 kDa were imported into both isolated mitochondria and mitochondria within human cells in culture. This was confirmed by using an ion-selective electrode to measure uptake of the ph-PNA conjugates; by cell fractionation in conjunction with immunoblotting; by confocal microscopy; by immunogold-electron microscopy; and by crosslinking ph-PNA conjugates to mitochondrial matrix proteins. In all cases dissipating the mitochondrial membrane potential with an uncoupler prevented ph-PNA uptake. The ph-PNA conjugate selectively inhibited the in vitro replication of DNA containing the A8344G point mutation that causes the human mtDNA disease 'myoclonic epilepsy and ragged red fibres' (MERRF) but not the wild-type sequence that differs at a single nucleotide position. Therefore these modified PNA oligomers retain their selective binding to DNA and the lipophilic cation delivers them to mitochondria within cells. When MERRF cells were incubated with the ph-PNA conjugate the ratio of MERRF to wild-type mtDNA was unaffected, even though the ph-PNA content of the mitochondria was sufficient to inhibit MERRF mtDNA replication in a cell-free system. This unexpected finding suggests that nucleic acid derivatives cannot bind their complementary sequences during mtDNA replication. In summary, we have developed a new strategy for targeting PNA oligomers to mitochondria and used it to determine the effects of PNA on mutated mtDNA replication in cells. This work presents new approaches for the manipulation of mtDNA replication and expression, and will assist in the development of therapies for mtDNA diseases. (+info)ATP-sensitive potassium channels in dopaminergic neurons: transducers of mitochondrial dysfunction. (2/884)
ATP-sensitive potassium (K(ATP)) channels directly couple the metabolic state of a cell to its electrical activity. Dopaminergic midbrain neurons express alternative types of K(ATP) channels mediating their differential response to mitochondrial complex I inhibition. Because reduced complex I activity is present in Parkinson's Disease, differential K(ATP) channel expression suggests a novel candidate mechanism for selective dopaminergic degeneration. (+info)Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies. (3/884)
OBJECTIVE: To evaluate the frequency of pathogenic mtDNA transfer RNA mutations and deletions in biochemically demonstrable respiratory chain (RC) deficiencies in paediatric and adult patients. METHODS: We screened for deletions and sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index patients with clinical symptoms suggestive of a mitochondrial disorder and with biochemically demonstrable RC deficiency in skeletal muscle. RESULTS: We found pathogenic mitochondrial DNA mutations in 29% of the patients. The detection rate was significantly higher in adults (48%) than in the paediatric group (18%). Only one pathogenic mutation was detected in the neonatal group. In addition, we describe seven novel transfer RNA sequence variations with unknown pathogenic relevance (six homoplasmic and one heteroplasmic) and 13 homoplasmic polymorphisms. One heteroplasmic transfer RNA(Leu(UUR)) A>G mutation at position 3274 is associated with a distinct neurological syndrome. CONCLUSIONS: We provide an estimation of the frequency of mitochondrial transfer RNA mutations and deletions in paediatric and adult patients with respiratory chain deficiencies. (+info)Nuclear genetic defects of oxidative phosphorylation. (4/884)
ATP generated by oxidative phosphorylation is necessary for the normal function of most cells in the body. Partial deficiencies in this system are an important cause of a large and diverse group of multisystem disorders. As both the nuclear and mitochondrial genomes encode structural components of the enzyme complexes of the oxidative phosphorylation system, the disorders can be transmitted either in a Mendelian fashion or maternally, or can occur as sporadic cases. Over the last 12 years more than 100 mutations have been uncovered in mtDNA, mostly associated with disease in the adult population. Recently, much attention has turned to the investigation of the nuclear oxidative phosphorylation gene defects. The majority of these are inherited as autosomal recessive traits, producing severe, and usually fatal disease in infants. Adult-onset Mendelian oxidative phosphorylation diseases, which can be inherited as autosomal recessive or dominant traits, have a milder phenotype, and most are associated with multiple mtDNA deletions. Approximately 20 different nuclear gene defects have now been identified in genes coding for structural components of the complexes, assembly/maintenance factors and factors necessary for the maintenance of mtDNA integrity. Some clear genotype-phenotype associations have emerged, and there is an unexpected link between some structural gene mutations and rare cancers, implicating mitochondria as oxygen sensors in the hypoxia response. (+info)In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness. (5/884)
Eukaryotic tRNAs are transcribed as precursors. A 5'-end leader and 3'-end trailer are endonucleolytically removed by RNase P and 3'-tRNase before 3'-end CCA addition, aminoacylation, nuclear export and translation. 3'-End -CC can be a 3'-tRNase anti-determinant with the ability to prevent mature tRNA from recycling through 3'-tRNase. Twenty-two tRNAs punctuate the two rRNAs and 13 mRNAs in long, bidirectional mitochondrial transcripts. Accurate mitochondrial gene expression thus depends on endonucleolytic excision of tRNAs. Various mitochondrial diseases and syndromes could arise from defective tRNA end processing. The U7445C substitution in the human mitochondrial L-strand transcript (U74C directly following the discriminator base of tRNA(Ser(UCN))) causes non-syndromic deafness. The sequence of the precursor (G/UCU) becomes G/CCU, resembling a 3'-tRNase anti-determinant. We demonstrate that a tRNA(Ser(UCN)) precursor with the U7445C substitution cannot be processed in vitro by 3'-tRNase from human mitochondria. A 3'-end processing defect in this tRNA precursor could thus be responsible for mitochondrial disease. (+info)Mitochondrial disease and stroke. (6/884)
BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged +info)Cardiac dysfunction in mice lacking cytochrome-c oxidase subunit VIaH. (7/884)
Cytochrome-c oxidase subunit VIaH (COXVIaH) has been implicated in the modulation of COX activity. A gene-targeting strategy was undertaken to generate mice that lacked COXVIaH to determine its role in regulation of oxidative energy production and mechanical performance in cardiac muscle. Total COX activity was decreased in hearts from mutant mice, which appears to be a consequence of altered assembly of the holoenzyme COX. However, total myocardial ATP was not significantly different in wild-type and mutant mice. Myocardial performance was examined using the isolated working heart preparation. As left atrial filling pressure increased, hearts from mutant mice were unable to generate equivalent stroke work compared with hearts from wild-type mice. Direct measurement of left ventricular end-diastolic volume using magnetic resonance imaging revealed that cardiac dysfunction was a consequence of impaired ventricular filling or diastolic dysfunction. These findings suggest that a genetic deficiency of COXVIaH has a measurable impact on myocardial diastolic performance despite the presence of normal cellular ATP levels. (+info)Inborn errors of complex II--unusual human mitochondrial diseases. (8/884)
The succinate dehydrogenase consists of only four subunits, all nuclearly encoded, and is part of both the respiratory chain and the Krebs cycle. Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase have been recently reported in human and shown to be associated with a wide spectrum of clinical presentations. Although a comparatively rare deficiency in human, molecularly defined succinate dehydrogenase deficiency has already been found to cause encephalomyopathy in childhood, optic atrophy or tumor in adulthood. Because none of the typical housekeeping genes encoding this respiratory chain complex is known to present tissue-specific isoforms, the tissue-specific involvement represents a quite intriguing question, which is mostly addressed in this review. A differential impairment of electron flow through the respiratory chain, handling of oxygen, and/or metabolic blockade possibly associated with defects in the different subunits that can be advocated to account for tissue-specific involvement is discussed. (+info)Mitochondrial diseases are a group of disorders caused by dysfunctions in the mitochondria, which are the energy-producing structures in cells. These diseases can affect people of any age and can manifest in various ways, depending on which organs or systems are affected. Common symptoms include muscle weakness, neurological problems, cardiac disease, diabetes, and vision/hearing loss. Mitochondrial diseases can be inherited from either the mother's or father's side, or they can occur spontaneously due to genetic mutations. They can range from mild to severe and can even be life-threatening in some cases.
Mitochondrial myopathies are a group of genetic disorders caused by mutations in the mitochondrial DNA or nuclear DNA that affect the function of the mitochondria, which are the energy-producing structures in cells. These mutations can result in impaired muscle function and other symptoms, depending on the specific type and severity of the disorder.
Mitochondrial myopathies can present at any age and can cause a range of symptoms, including muscle weakness, exercise intolerance, fatigue, muscle pain, and difficulty with coordination and balance. Some people with mitochondrial myopathies may also experience neurological symptoms such as seizures, developmental delays, and hearing or vision loss.
The diagnosis of mitochondrial myopathies typically involves a combination of clinical evaluation, muscle biopsy, genetic testing, and other diagnostic tests to assess mitochondrial function. Treatment is generally supportive and may include physical therapy, medications to manage symptoms, and nutritional support. In some cases, specific therapies such as vitamin or coenzyme Q10 supplementation may be recommended based on the underlying genetic defect.
Mitochondrial Encephalomyopathies are a group of genetic disorders that primarily affect the mitochondria, which are the energy-producing structures in cells. "Encephalo" refers to the brain, while "myopathy" refers to muscle disease. Therefore, Mitochondrial Encephalomyopathies are conditions that cause both neurological and muscular symptoms due to impaired mitochondrial function.
These disorders can affect any organ in the body, but they primarily impact the brain, nerves, and muscles. Symptoms may include muscle weakness, seizures, developmental delays, hearing loss, vision loss, heart problems, and lactic acidosis (a buildup of lactic acid in the blood).
Mitochondrial Encephalomyopathies can be caused by mutations in either the mitochondrial DNA or nuclear DNA. They are often inherited from the mother, as mitochondria are passed down through the maternal line. However, some cases can also result from new mutations that occur spontaneously.
Due to the complex nature of these disorders and their varying symptoms, diagnosis and treatment can be challenging. Treatment typically focuses on managing specific symptoms and may include medications, dietary changes, and physical therapy.
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare inherited mitochondrial disorder that affects the body's energy production mechanisms. It is characterized by a combination of symptoms including recurrent headaches, vomiting, seizures, vision loss, hearing impairment, muscle weakness, and stroke-like episodes affecting primarily young adults.
The condition is caused by mutations in the mitochondrial DNA (mtDNA), most commonly the A3243G point mutation in the MT-TL1 gene. The symptoms of MELAS syndrome can vary widely among affected individuals, even within the same family, due to the complex inheritance pattern of mtDNA.
MELAS syndrome is typically diagnosed based on a combination of clinical features, laboratory tests, and genetic testing. Treatment is supportive and aimed at managing individual symptoms as they arise.
Mitochondrial DNA (mtDNA) is the genetic material present in the mitochondria, which are specialized structures within cells that generate energy. Unlike nuclear DNA, which is present in the cell nucleus and inherited from both parents, mtDNA is inherited solely from the mother.
MtDNA is a circular molecule that contains 37 genes, including 13 genes that encode for proteins involved in oxidative phosphorylation, a process that generates energy in the form of ATP. The remaining genes encode for rRNAs and tRNAs, which are necessary for protein synthesis within the mitochondria.
Mutations in mtDNA can lead to a variety of genetic disorders, including mitochondrial diseases, which can affect any organ system in the body. These mutations can also be used in forensic science to identify individuals and establish biological relationships.
Myoclonic Epilepsy with Ragged Red Fibers (MERRF) is a rare mitochondrial disorder, which is a group of genetic disorders that affect the energy production within cells. It is characterized by multiple symptoms including myoclonus (jerky, involuntary muscle spasms), epilepsy (recurrent seizures), ataxia (lack of coordination and balance), dementia, and weakness. The name "MERRF" comes from the characteristic finding of "ragged red fibers" in muscle biopsies when viewed under a microscope using special stains. These fibers are abnormal muscle cells containing clusters of abnormal mitochondria. MERRF is caused by mutations in the mitochondrial DNA, most commonly the A8344G point mutation in the MT-TK gene. It is typically inherited from the mother and can affect multiple organs throughout the body.
Kearns-Sayre Syndrome (KSS) is a rare, progressive genetic disorder that affects the function of the mitochondria, which are the energy-producing structures in cells. It is classified as a type of mitochondrial myopathy and is typically associated with symptoms that appear before the age of 20.
The medical definition of Kearns-Sayre Syndrome includes the following criteria:
1. Onset before 20 years of age
2. Progressive external ophthalmoplegia (PEO), which is characterized by weakness and paralysis of the eye muscles, leading to drooping eyelids (ptosis) and limited eye movement
3. Retinitis pigmentosa, a degenerative condition affecting the retina that can lead to vision loss
4. A cardiac conduction defect, such as heart block
5. Ragged red fibers on muscle biopsy
6. At least one major criteria or two minor criteria must be present:
* Major criteria include cerebellar ataxia (lack of coordination), deafness, or increased protein in the cerebrospinal fluid
* Minor criteria include pigmentary retinopathy, heart block, or a high level of creatine kinase in the blood.
Kearns-Sayre Syndrome is caused by a single large-scale deletion of genes in the mitochondrial DNA and is usually sporadic, meaning it occurs randomly and is not inherited from parents. The condition can be diagnosed through genetic testing, muscle biopsy, or other clinical tests. Treatment is focused on managing symptoms and may include physical therapy, surgery for ptosis, hearing aids, and pacemakers for heart block.
Chronic Progressive External Ophthalmoplegia (CPEO) is a rare, progressive neuromuscular disorder that affects the extraocular muscles, which are responsible for eye movement. This results in progressive weakness and paralysis of these muscles, leading to limitations in eye movement and, subsequently, binocular vision.
The term "chronic" refers to the slow, gradual progression of symptoms over time, while "progressive" highlights the worsening nature of the condition. "External" indicates that the extraocular muscles are involved, as opposed to the "internal" ophthalmoplegia, which would refer to the paralysis of the iris and ciliary body muscles within the eye.
CPEO is characterized by symmetrical, bilateral paresis (partial paralysis) or complete paralysis of the extraocular muscles, leading to drooping eyelids (ptosis), limited eye movements in all directions, and double vision (diplopia). The onset of symptoms typically occurs during adulthood, but it can also manifest in childhood.
CPEO is often associated with mitochondrial DNA abnormalities or mutations, which can lead to impaired energy production within the cells. This specific type of ophthalmoplegia is generally not linked to other neurological or systemic symptoms, but it can co-occur with additional manifestations in some cases, forming a broader spectrum of mitochondrial disorders known as Kearns-Sayre syndrome (KSS) or oculocraniosomatic syndrome.
There is no cure for CPEO, and management primarily focuses on addressing the symptoms and improving quality of life. Treatment options may include surgical interventions to correct ptosis or strabismus (squint), as well as supportive care such as visual aids and rehabilitation strategies.
A transfer RNA (tRNA) molecule that carries the amino acid leucine is referred to as "tRNA-Leu." This specific tRNA molecule recognizes and binds to a codon (a sequence of three nucleotides in mRNA) during protein synthesis or translation. In this case, tRNA-Leu can recognize and pair with any of the following codons: UUA, UUG, CUU, CUC, CUA, and CUG. Once bound to the mRNA at the ribosome, leucine is added to the growing polypeptide chain through the action of aminoacyl-tRNA synthetase enzymes that catalyze the attachment of specific amino acids to their corresponding tRNAs. This ensures the accurate and efficient production of proteins based on genetic information encoded in mRNA.
Diffuse cerebral sclerosis of Schilder, also known as Schilder's disease, is a rare inflammatory demyelinating disorder of the central nervous system. It primarily affects children and young adults, but can occur at any age. The condition is characterized by widespread destruction of the myelin sheath, which surrounds and protects nerve fibers in the brain.
The hallmark feature of Schilder's disease is the presence of multiple, large, symmetrical lesions in the white matter of both cerebral hemispheres. These lesions are typically located in the parieto-occipital regions of the brain and can extend to involve other areas as well.
The symptoms of Schilder's disease vary depending on the location and extent of the lesions, but may include:
* Progressive intellectual decline
* Seizures
* Visual disturbances
* Weakness or paralysis on one side of the body (hemiparesis)
* Loss of sensation in various parts of the body
* Speech difficulties
* Behavioral changes, such as irritability, mood swings, and depression
The exact cause of Schilder's disease is not known, but it is believed to be an autoimmune disorder, in which the body's own immune system mistakenly attacks the myelin sheath. There is no cure for Schilder's disease, and treatment typically involves corticosteroids or other immunosuppressive therapies to reduce inflammation and slow the progression of the disease. Despite treatment, many patients with Schilder's disease experience significant disability and may require long-term care.
Leigh Disease, also known as Subacute Necrotizing Encephalomyelopathy (SNE), is a rare inherited neurometabolic disorder that affects the central nervous system. It is characterized by progressive degeneration of the brain and spinal cord. The condition typically appears in infancy or early childhood, although it can develop in adolescence or adulthood.
Leigh Disease is caused by mutations in mitochondrial DNA or nuclear genes that disrupt the function of the oxidative phosphorylation system, a part of the cellular energy production process. This results in decreased ATP (adenosine triphosphate) production and an accumulation of lactic acid in the body.
The symptoms of Leigh Disease can vary widely but often include vomiting, seizures, developmental delays, muscle weakness, loss of muscle tone, and difficulty swallowing and breathing. The condition can also cause lesions to form on the brainstem and basal ganglia, which can lead to further neurological problems.
There is no cure for Leigh Disease, and treatment is focused on managing symptoms and supporting affected individuals as they cope with the progression of the disease.
Mitochondrial genes are a type of gene that is located in the DNA (deoxyribonucleic acid) found in the mitochondria, which are small organelles present in the cytoplasm of eukaryotic cells (cells with a true nucleus). Mitochondria are responsible for generating energy for the cell through a process called oxidative phosphorylation.
The human mitochondrial genome is a circular DNA molecule that contains 37 genes, including 13 genes that encode for proteins involved in oxidative phosphorylation, 22 genes that encode for transfer RNAs (tRNAs), and 2 genes that encode for ribosomal RNAs (rRNAs). Mutations in mitochondrial genes can lead to a variety of inherited mitochondrial disorders, which can affect any organ system in the body and can present at any age.
Mitochondrial DNA is maternally inherited, meaning that it is passed down from the mother to her offspring through the egg cell. This is because during fertilization, only the sperm's nucleus enters the egg, while the mitochondria remain outside. As a result, all of an individual's mitochondrial DNA comes from their mother.
Cytochrome-c oxidase deficiency is a genetic disorder that affects the function of the mitochondria, which are the energy-producing structures in cells. Specifically, it is a deficiency in cytochrome-c oxidase (COX), also known as complex IV, which is an enzyme located in the inner membrane of the mitochondria that plays a critical role in the electron transport chain and oxidative phosphorylation.
Cytochrome-c oxidase deficiency can be caused by mutations in any of the genes that encode the subunits or assembly factors of COX. The severity of the disorder and the specific symptoms can vary widely, depending on the extent of the enzyme deficiency and the particular tissues and organs that are affected.
Symptoms of cytochrome-c oxidase deficiency may include muscle weakness, developmental delay, hypotonia (low muscle tone), seizures, lactic acidosis, and cardiac and neurological problems. In some cases, the disorder can be life-threatening in infancy or early childhood.
There is no cure for cytochrome-c oxidase deficiency, and treatment is generally supportive and aimed at addressing specific symptoms. Antioxidant therapy, such as vitamin C and E supplements, may help to reduce oxidative stress and improve mitochondrial function in some cases. In severe cases, a heart or liver transplant may be considered.
Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).
Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.
Electron Transport Complex I, also known as NADH:ubiquinone oxidoreductase, is a large protein complex located in the inner mitochondrial membrane of eukaryotic cells and the cytoplasmic membrane of prokaryotic cells. It is the first complex in the electron transport chain, a series of protein complexes that transfer electrons from NADH to oxygen, driving the synthesis of ATP through chemiosmosis.
Complex I consists of multiple subunits, including a flavin mononucleotide (FMN) cofactor and several iron-sulfur clusters, which facilitate the oxidation of NADH and the reduction of ubiquinone (coenzyme Q). The energy released during this electron transfer process is used to pump protons across the membrane, creating a proton gradient that drives ATP synthesis.
Defects in Complex I can lead to various mitochondrial diseases, including neurological disorders and muscle weakness.
Oxidative phosphorylation is the metabolic process by which cells use enzymes to generate energy in the form of adenosine triphosphate (ATP) from the oxidation of nutrients, such as glucose or fatty acids. This process occurs in the inner mitochondrial membrane of eukaryotic cells and is facilitated by the electron transport chain, which consists of a series of protein complexes that transfer electrons from donor molecules to acceptor molecules. As the electrons are passed along the chain, they release energy that is used to pump protons across the membrane, creating a gradient. The ATP synthase enzyme then uses the flow of protons back across the membrane to generate ATP, which serves as the main energy currency for cellular processes.
Electron Transport Complex IV is also known as Cytochrome c oxidase. It is the last complex in the electron transport chain, located in the inner mitochondrial membrane of eukaryotic cells and the plasma membrane of prokaryotic cells. This complex contains 13 subunits, two heme groups (a and a3), and three copper centers (A, B, and C).
In the electron transport chain, Complex IV receives electrons from cytochrome c and transfers them to molecular oxygen, reducing it to water. This process is accompanied by the pumping of protons across the membrane, contributing to the generation of a proton gradient that drives ATP synthesis via ATP synthase (Complex V). The overall reaction catalyzed by Complex IV can be summarized as follows:
4e- + 4H+ + O2 → 2H2O
Defects in Cytochrome c oxidase can lead to various diseases, including mitochondrial encephalomyopathies and neurodegenerative disorders.
Ubiquinone, also known as coenzyme Q10 (CoQ10), is a lipid-soluble benzoquinone that plays a crucial role in the mitochondrial electron transport chain as an essential component of Complexes I, II, and III. It functions as an electron carrier, assisting in the transfer of electrons from reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) to molecular oxygen during oxidative phosphorylation, thereby contributing to the generation of adenosine triphosphate (ATP), the primary energy currency of the cell.
Additionally, ubiquinone acts as a potent antioxidant in both membranes and lipoproteins, protecting against lipid peroxidation and oxidative damage to proteins and DNA. Its antioxidant properties stem from its ability to donate electrons and regenerate other antioxidants like vitamin E. Ubiquinone is synthesized endogenously in all human cells, with the highest concentrations found in tissues with high energy demands, such as the heart, liver, kidneys, and skeletal muscles.
Deficiency in ubiquinone can result from genetic disorders, aging, or certain medications (such as statins), leading to impaired mitochondrial function and increased oxidative stress. Supplementation with ubiquinone has been explored as a potential therapeutic strategy for various conditions associated with mitochondrial dysfunction and oxidative stress, including cardiovascular diseases, neurodegenerative disorders, and cancer.
Metabolic brain diseases are a group of disorders caused by genetic defects that affect the body's metabolism and result in abnormal accumulation of harmful substances in the brain. These conditions are present at birth (inborn) or develop during infancy or early childhood. Examples of metabolic brain diseases that are present at birth include:
1. Phenylketonuria (PKU): A disorder caused by a deficiency of the enzyme phenylalanine hydroxylase, which leads to an accumulation of phenylalanine in the brain and can cause intellectual disability, seizures, and behavioral problems if left untreated.
2. Maple syrup urine disease (MSUD): A disorder caused by a deficiency of the enzyme branched-chain ketoacid dehydrogenase, which leads to an accumulation of branched-chain amino acids in the body and can cause intellectual disability, seizures, and metabolic crisis if left untreated.
3. Urea cycle disorders: A group of disorders caused by defects in enzymes that help remove ammonia from the body. Accumulation of ammonia in the blood can lead to brain damage, coma, or death if not treated promptly.
4. Organic acidemias: A group of disorders caused by defects in enzymes that help break down certain amino acids and other organic compounds. These conditions can cause metabolic acidosis, seizures, and developmental delays if left untreated.
Early diagnosis and treatment of these conditions are crucial to prevent irreversible brain damage and other complications. Treatment typically involves dietary restrictions, supplements, and medications to manage the underlying metabolic imbalance. In some cases, enzyme replacement therapy or liver transplantation may be necessary.
Mitochondria in muscle, also known as the "powerhouses" of the cell, are organelles that play a crucial role in generating energy for muscle cells through a process called cellular respiration. They convert the chemical energy found in glucose and oxygen into ATP (adenosine triphosphate), which is the main source of energy used by cells.
Muscle cells contain a high number of mitochondria due to their high energy demands for muscle contraction and relaxation. The number and size of mitochondria in muscle fibers can vary depending on the type of muscle fiber, with slow-twitch, aerobic fibers having more numerous and larger mitochondria than fast-twitch, anaerobic fibers.
Mitochondrial dysfunction has been linked to various muscle disorders, including mitochondrial myopathies, which are characterized by muscle weakness, exercise intolerance, and other symptoms related to impaired energy production in the muscle cells.
A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.
Mitochondrial proteins are any proteins that are encoded by the nuclear genome or mitochondrial genome and are located within the mitochondria, an organelle found in eukaryotic cells. These proteins play crucial roles in various cellular processes including energy production, metabolism of lipids, amino acids, and steroids, regulation of calcium homeostasis, and programmed cell death or apoptosis.
Mitochondrial proteins can be classified into two main categories based on their origin:
1. Nuclear-encoded mitochondrial proteins (NEMPs): These are proteins that are encoded by genes located in the nucleus, synthesized in the cytoplasm, and then imported into the mitochondria through specific import pathways. NEMPs make up about 99% of all mitochondrial proteins and are involved in various functions such as oxidative phosphorylation, tricarboxylic acid (TCA) cycle, fatty acid oxidation, and mitochondrial dynamics.
2. Mitochondrial DNA-encoded proteins (MEPs): These are proteins that are encoded by the mitochondrial genome, synthesized within the mitochondria, and play essential roles in the electron transport chain (ETC), a key component of oxidative phosphorylation. The human mitochondrial genome encodes only 13 proteins, all of which are subunits of complexes I, III, IV, and V of the ETC.
Defects in mitochondrial proteins can lead to various mitochondrial disorders, which often manifest as neurological, muscular, or metabolic symptoms due to impaired energy production. These disorders are usually caused by mutations in either nuclear or mitochondrial genes that encode mitochondrial proteins.
Lactic acidosis is a medical condition characterized by an excess accumulation of lactic acid in the body. Lactic acid is a byproduct produced in the muscles and other tissues during periods of low oxygen supply or increased energy demand. Under normal circumstances, lactic acid is quickly metabolized and cleared from the body. However, when the production of lactic acid exceeds its clearance, it can lead to a state of acidosis, where the pH of the blood becomes too acidic.
Lactic acidosis can be caused by several factors, including:
* Prolonged exercise or strenuous physical activity
* Severe illness or infection
* Certain medications, such as metformin and isoniazid
* Alcoholism
* Hypoxia (low oxygen levels) due to lung disease, heart failure, or anemia
* Inherited metabolic disorders that affect the body's ability to metabolize lactic acid
Symptoms of lactic acidosis may include rapid breathing, fatigue, muscle weakness, nausea, vomiting, and abdominal pain. Severe cases can lead to coma, organ failure, and even death. Treatment typically involves addressing the underlying cause of the condition and providing supportive care, such as administering intravenous fluids and bicarbonate to help restore normal pH levels.
The exome is the part of the genome that contains all the protein-coding regions. It represents less than 2% of the human genome but accounts for about 85% of disease-causing mutations. Exome sequencing, therefore, is a cost-effective and efficient method to identify genetic variants associated with various diseases, including cancer, neurological disorders, and inherited genetic conditions.
Photobiology is the study of the interactions between non-ionizing radiation, primarily ultraviolet (UV), visible, and infrared radiation, and living organisms. It involves how these radiations affect organisms, their metabolic processes, and biological rhythms. This field also includes research on the use of light in therapy, such as phototherapy for treating various skin conditions and mood disorders. Photobiology has important implications for understanding the effects of sunlight on human health, including both beneficial and harmful effects.
Hereditary Optic Atrophy, Leber type (LOA) is a mitochondrial DNA-associated inherited condition that primarily affects the optic nerve and leads to vision loss. It is characterized by the degeneration of retinal ganglion cells and their axons, which make up the optic nerve. This results in bilateral, painless, and progressive visual deterioration, typically beginning in young adulthood (14-35 years).
Leber's hereditary optic atrophy is caused by mutations in the mitochondrial DNA (mtDNA) gene MT-ND4 or MT-ND6. The condition follows a maternal pattern of inheritance, meaning that it is passed down through the mother's lineage.
The onset of LOA usually occurs in one eye first, followed by the second eye within weeks to months. Central vision is initially affected, leading to blurriness and loss of visual acuity. Color vision may also be impaired. The progression of the condition generally stabilizes after a few months, but complete recovery of vision is unlikely.
Currently, there is no cure for Leber's hereditary optic atrophy. Treatment focuses on managing symptoms and providing visual rehabilitation to help affected individuals adapt to their visual impairment.
NADH dehydrogenase, also known as Complex I, is an enzyme complex in the electron transport chain located in the inner mitochondrial membrane. It catalyzes the oxidation of NADH to NAD+ and the reduction of coenzyme Q to ubiquinol, playing a crucial role in cellular respiration and energy production. The reaction involves the transfer of electrons from NADH to coenzyme Q, which contributes to the generation of a proton gradient across the membrane, ultimately leading to ATP synthesis. Defects in NADH dehydrogenase can result in various mitochondrial diseases and disorders.
Myalgia is a medical term that refers to muscle pain or inflammation in the soft tissues of the body. The pain can be acute, occurring suddenly and lasting for a few days, or chronic, persisting over a longer period of time. Myalgia can affect any muscle in the body, but it is most commonly experienced in the neck, back, and extremities.
The causes of myalgia are varied and can include injury, overuse, infection, inflammation, or neurological conditions. Common causes of myalgia include fibromyalgia, polymyositis, dermatomyositis, and infections such as influenza or Lyme disease.
Treatment for myalgia depends on the underlying cause of the muscle pain. Rest, physical therapy, stretching exercises, and over-the-counter pain relievers may be sufficient for mild cases of myalgia. In more severe cases, prescription medications, injections, or other therapies may be necessary to manage the pain and address any underlying medical conditions.
Cell respiration is the process by which cells convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The three main stages of cell respiration are glycolysis, the citric acid cycle (also known as the Krebs cycle), and the electron transport chain.
During glycolysis, which takes place in the cytoplasm, glucose is broken down into two molecules of pyruvate, producing a small amount of ATP and reducing power in the form of NADH.
The citric acid cycle occurs in the mitochondria and involves the breakdown of acetyl-CoA (formed from pyruvate) to produce more ATP, NADH, and FADH2.
Finally, the electron transport chain, also located in the mitochondria, uses the energy from NADH and FADH2 to pump protons across the inner mitochondrial membrane, creating a proton gradient. The flow of protons back across the membrane drives the synthesis of ATP, which is used as a source of energy by the cell.
Cell respiration is a crucial process that allows cells to generate the energy they need to perform various functions and maintain homeostasis.
Mitochondrial proton-translocating ATPases, also known as F1F0-ATP synthase or complex V, are enzyme complexes found in the inner mitochondrial membrane of eukaryotic cells. They play a crucial role in the process of oxidative phosphorylation, which generates ATP (adenosine triphosphate), the primary energy currency of the cell.
These enzyme complexes consist of two main parts: F1 and F0. The F1 portion is located on the matrix side of the inner mitochondrial membrane and contains the catalytic sites for ATP synthesis. It is composed of three α, three β, and one γ subunits, along with additional subunits that regulate its activity.
The F0 portion spans the inner mitochondrial membrane and functions as a proton channel. It is composed of multiple subunits, including a, b, and c subunits, which form a rotor-stator structure. As protons flow through this channel due to the electrochemical gradient established by the electron transport chain, the rotation of the F0 rotor drives the synthesis of ATP in the F1 portion.
Mitochondrial proton-translocating ATPases are highly conserved across different species and play a vital role in maintaining energy homeostasis within the cell. Dysfunction in these enzyme complexes can lead to various mitochondrial disorders and diseases, such as neurodegenerative disorders, muscle weakness, and metabolic abnormalities.
A point mutation is a type of genetic mutation where a single nucleotide base (A, T, C, or G) in DNA is altered, deleted, or substituted with another nucleotide. Point mutations can have various effects on the organism, depending on the location of the mutation and whether it affects the function of any genes. Some point mutations may not have any noticeable effect, while others might lead to changes in the amino acids that make up proteins, potentially causing diseases or altering traits. Point mutations can occur spontaneously due to errors during DNA replication or be inherited from parents.
Intestinal pseudo-obstruction, also known as paralytic ileus or functional obstruction, is a gastrointestinal motility disorder characterized by the absence of mechanical obstruction in the intestines, but with symptoms mimicking a mechanical small bowel obstruction. These symptoms may include abdominal distention, cramping, nausea, vomiting, and constipation or difficulty passing stools.
The condition is caused by impaired intestinal motility due to dysfunction of the nerves or muscles that control the movement of food and waste through the digestive system. It can be a chronic or acute condition and may occur as a primary disorder or secondary to other medical conditions, such as surgery, trauma, infections, metabolic disorders, neurological diseases, or certain medications.
Diagnosis of intestinal pseudo-obstruction typically involves imaging studies, such as X-rays or CT scans, to rule out mechanical obstruction and confirm the presence of dilated bowel loops. Manometry and other specialized tests may also be used to assess intestinal motility. Treatment options include medications to stimulate intestinal motility, dietary modifications, and in severe cases, surgery or intravenous nutrition.
Dichloroacetic acid (DCA) is a chemical compound with the formula CCl2CO2H. It is a colorless liquid that is used as a reagent in organic synthesis and as a laboratory research tool. DCA is also a byproduct of water chlorination and has been found to occur in low levels in some chlorinated drinking waters.
In the medical field, DCA has been studied for its potential anticancer effects. Preclinical studies have suggested that DCA may be able to selectively kill cancer cells by inhibiting the activity of certain enzymes involved in cell metabolism. However, more research is needed to determine whether DCA is safe and effective as a cancer treatment in humans.
It is important to note that DCA is not currently approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) for use as a cancer treatment. It should only be used in clinical trials or under the supervision of a qualified healthcare professional.
In the context of medical terminology, a "habit" refers to a regular, repeated behavior or practice that is often performed automatically or subconsciously. Habits can be physical (such as biting nails) or mental (such as worrying). They can be harmless, beneficial (like regularly brushing your teeth), or harmful (like smoking cigarettes).
Habits are different from instincts or reflexes because they involve a learned behavior that has been repeated and reinforced over time. Breaking a habit can often be challenging due to the deeply ingrained nature of the behavior.
A phenotype is the physical or biochemical expression of an organism's genes, or the observable traits and characteristics resulting from the interaction of its genetic constitution (genotype) with environmental factors. These characteristics can include appearance, development, behavior, and resistance to disease, among others. Phenotypes can vary widely, even among individuals with identical genotypes, due to differences in environmental influences, gene expression, and genetic interactions.
A mitochondrial genome refers to the genetic material present in the mitochondria, which are small organelles found in the cytoplasm of eukaryotic cells (cells with a true nucleus). The mitochondrial genome is typically circular and contains a relatively small number of genes compared to the nuclear genome.
Mitochondrial DNA (mtDNA) encodes essential components of the electron transport chain, which is vital for cellular respiration and energy production. MtDNA also contains genes that code for some mitochondrial tRNAs and rRNAs needed for protein synthesis within the mitochondria.
In humans, the mitochondrial genome is about 16.6 kilobases in length and consists of 37 genes: 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes. The mitochondrial genome is inherited maternally, as sperm contribute very few or no mitochondria during fertilization. Mutations in the mitochondrial genome can lead to various genetic disorders, often affecting tissues with high energy demands, such as muscle and nerve cells.
Electron Transport Complex II, also known as succinate-Q oxidoreductase, is a key component of the electron transport chain in the inner mitochondrial membrane. It plays a crucial role in the process of cellular respiration, where it facilitates the transfer of electrons from succinate to ubiquinone (Q), thereby generating a proton gradient across the membrane. This gradient drives the synthesis of ATP, which is the primary source of energy for the cell.
The complex is composed of four core subunits: flavoprotein (Fp), iron-sulfur protein (Ip), cytochrome b (Cyb), and ubiquinone-binding protein (Qp). Electrons from succinate are accepted by FAD in the Fp subunit, and then transferred to the Ip subunit containing iron-sulfur clusters. From there, the electrons are moved to heme groups in the Cyb subunit, and finally passed on to ubiquinone at the Qp subunit.
In addition to its role in the electron transport chain, Complex II has been implicated in various cellular processes such as regulation of reactive oxygen species (ROS) production and modulation of apoptosis. Mutations in genes encoding Complex II subunits have been associated with several human diseases, including neurodegenerative disorders and cancer.
Succinate dehydrogenase (SDH) is an enzyme complex that plays a crucial role in the process of cellular respiration, specifically in the citric acid cycle (also known as the Krebs cycle) and the electron transport chain. It is located in the inner mitochondrial membrane of eukaryotic cells.
SDH catalyzes the oxidation of succinate to fumarate, converting it into a molecule of fadaquate in the process. During this reaction, two electrons are transferred from succinate to the FAD cofactor within the SDH enzyme complex, reducing it to FADH2. These electrons are then passed on to ubiquinone (CoQ), which is a mobile electron carrier in the electron transport chain, leading to the generation of ATP, the main energy currency of the cell.
SDH is also known as mitochondrial complex II because it is the second complex in the electron transport chain. Mutations in the genes encoding SDH subunits or associated proteins have been linked to various human diseases, including hereditary paragangliomas, pheochromocytomas, gastrointestinal stromal tumors (GISTs), and some forms of neurodegenerative disorders.
Polarography is a type of electrochemical analysis technique used to determine the concentration of an ion or electron-transferring species in a solution. It involves measuring the current that flows through an electrode as the voltage is varied, which can provide information about the redox potential and the number of electrons transferred during a reaction. The technique is particularly useful for analyzing complex mixtures and for detecting trace amounts of substances.
In polarography, a dropping mercury electrode (DME) is typically used as the working electrode. As the mercury droplets fall from the electrode, they create fresh surfaces for analysis, which helps to minimize interference from surface-adsorbed species. The DME is immersed in a solution containing the analyte along with a supporting electrolyte, and a potential is applied between the DME and a reference electrode.
As the potential is scanned, reduction or oxidation of the analyte occurs at the DME surface, leading to a current that can be measured. The resulting polarogram (a plot of current vs. voltage) shows peaks or waves corresponding to the redox potentials of the analyte, which can be used to identify and quantify the species present in the solution.
Polarography is a sensitive and selective technique that has been widely used in fields such as environmental analysis, pharmaceuticals, and biochemistry. However, it has largely been replaced by more modern electrochemical techniques, such as cyclic voltammetry and differential pulse voltammetry, which offer higher sensitivity and better resolution of complex mixtures.
DNA-directed DNA polymerase is a type of enzyme that synthesizes new strands of DNA by adding nucleotides to an existing DNA template in a 5' to 3' direction. These enzymes are essential for DNA replication, repair, and recombination. They require a single-stranded DNA template, a primer with a free 3' hydroxyl group, and the four deoxyribonucleoside triphosphates (dNTPs) as substrates to carry out the polymerization reaction.
DNA polymerases also have proofreading activity, which allows them to correct errors that occur during DNA replication by removing mismatched nucleotides and replacing them with the correct ones. This helps ensure the fidelity of the genetic information passed from one generation to the next.
There are several different types of DNA polymerases, each with specific functions and characteristics. For example, DNA polymerase I is involved in both DNA replication and repair, while DNA polymerase III is the primary enzyme responsible for DNA replication in bacteria. In eukaryotic cells, DNA polymerase alpha, beta, gamma, delta, and epsilon have distinct roles in DNA replication, repair, and maintenance.
I'm happy to help! Here are the definitions for each of those terms:
1. RNA (Ribonucleic Acid): RNA is a nucleic acid that plays a crucial role in the process of gene expression. It carries genetic information from DNA to the ribosomes, where proteins are synthesized. RNA is made up of a long chain of nucleotides, just like DNA, but with some key differences in its structure and composition.
2. Transfer: In the context of biochemistry, "transfer" refers to the movement or transport of molecules from one location to another within a cell or between cells. This process is often facilitated by specific proteins or other molecular carriers.
3. Lys (Lysine): Lysine is an essential amino acid that cannot be synthesized by the human body and must be obtained through diet. It plays important roles in various biological processes, including protein synthesis, enzyme function, hormone production, and energy metabolism. In molecular biology, lysine is often used as a marker for certain types of modifications to proteins or nucleic acids.
Therefore, "RNA, Transfer, Lys" could refer to the transfer RNA (tRNA) molecule that carries a specific amino acid, such as lysine, to the ribosome during protein synthesis. The tRNA molecule recognizes a specific codon on the messenger RNA (mRNA) and brings the corresponding amino acid to the growing polypeptide chain, allowing for the translation of genetic information into a functional protein.
Spinocerebellar degenerations (SCDs) are a group of genetic disorders that primarily affect the cerebellum, the part of the brain responsible for coordinating muscle movements, and the spinal cord. These conditions are characterized by progressive degeneration or loss of nerve cells in the cerebellum and/or spinal cord, leading to various neurological symptoms.
SCDs are often inherited in an autosomal dominant manner, meaning that only one copy of the altered gene from either parent is enough to cause the disorder. The most common type of SCD is spinocerebellar ataxia (SCA), which includes several subtypes (SCA1, SCA2, SCA3, etc.) differentiated by their genetic causes and specific clinical features.
Symptoms of spinocerebellar degenerations may include:
1. Progressive ataxia (loss of coordination and balance)
2. Dysarthria (speech difficulty)
3. Nystagmus (involuntary eye movements)
4. Oculomotor abnormalities (problems with eye movement control)
5. Tremors or other involuntary muscle movements
6. Muscle weakness and spasticity
7. Sensory disturbances, such as numbness or tingling sensations
8. Dysphagia (difficulty swallowing)
9. Cognitive impairment in some cases
The age of onset, severity, and progression of symptoms can vary significantly among different SCD subtypes and individuals. Currently, there is no cure for spinocerebellar degenerations, but various supportive treatments and therapies can help manage symptoms and improve quality of life.
Ophthalmoplegia is a medical term that refers to the paralysis or weakness of the eye muscles, which can result in double vision (diplopia) or difficulty moving the eyes. It can be caused by various conditions, including nerve damage, muscle disorders, or neurological diseases such as myasthenia gravis or multiple sclerosis. Ophthalmoplegia can affect one or more eye muscles and can be partial or complete. Depending on the underlying cause, ophthalmoplegia may be treatable with medications, surgery, or other interventions.
The Electron Transport Chain (ETC) is a series of complexes in the inner mitochondrial membrane that are involved in the process of cellular respiration. It is the final pathway for electrons derived from the oxidation of nutrients such as glucose, fatty acids, and amino acids to be transferred to molecular oxygen. This transfer of electrons drives the generation of a proton gradient across the inner mitochondrial membrane, which is then used by ATP synthase to produce ATP, the main energy currency of the cell.
The electron transport chain consists of four complexes (I-IV) and two mobile electron carriers (ubiquinone and cytochrome c). Electrons from NADH and FADH2 are transferred to Complex I and Complex II respectively, which then pass them along to ubiquinone. Ubiquinone then transfers the electrons to Complex III, which passes them on to cytochrome c. Finally, cytochrome c transfers the electrons to Complex IV, where they combine with oxygen and protons to form water.
The transfer of electrons through the ETC is accompanied by the pumping of protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient. The flow of protons back across the inner membrane through ATP synthase drives the synthesis of ATP from ADP and inorganic phosphate.
Overall, the electron transport chain is a crucial process for generating energy in the form of ATP in the cell, and it plays a key role in many metabolic pathways.
Muscular diseases, also known as myopathies, refer to a group of conditions that affect the functionality and health of muscle tissue. These diseases can be inherited or acquired and may result from inflammation, infection, injury, or degenerative processes. They can cause symptoms such as weakness, stiffness, cramping, spasms, wasting, and loss of muscle function.
Examples of muscular diseases include:
1. Duchenne Muscular Dystrophy (DMD): A genetic disorder that results in progressive muscle weakness and degeneration due to a lack of dystrophin protein.
2. Myasthenia Gravis: An autoimmune disease that causes muscle weakness and fatigue, typically affecting the eyes and face, throat, and limbs.
3. Inclusion Body Myositis (IBM): A progressive muscle disorder characterized by muscle inflammation and wasting, typically affecting older adults.
4. Polymyositis: An inflammatory myopathy that causes muscle weakness and inflammation throughout the body.
5. Metabolic Myopathies: A group of inherited disorders that affect muscle metabolism, leading to exercise intolerance, muscle weakness, and other symptoms.
6. Muscular Dystonias: Involuntary muscle contractions and spasms that can cause abnormal postures or movements.
It is important to note that muscular diseases can have a significant impact on an individual's quality of life, mobility, and overall health. Proper diagnosis and treatment are crucial for managing symptoms and improving outcomes.
Inborn errors of metabolism (IEM) refer to a group of genetic disorders caused by defects in enzymes or transporters that play a role in the body's metabolic processes. These disorders result in the accumulation or deficiency of specific chemicals within the body, which can lead to various clinical manifestations, such as developmental delay, intellectual disability, seizures, organ damage, and in some cases, death.
Examples of IEM include phenylketonuria (PKU), maple syrup urine disease (MSUD), galactosemia, and glycogen storage diseases, among many others. These disorders are typically inherited in an autosomal recessive manner, meaning that an affected individual has two copies of the mutated gene, one from each parent.
Early diagnosis and management of IEM are crucial to prevent or minimize complications and improve outcomes. Treatment options may include dietary modifications, supplementation with missing enzymes or cofactors, medication, and in some cases, stem cell transplantation or gene therapy.
Sideroblastic anemia is a type of anemia characterized by the presence of ringed sideroblasts in the bone marrow. Ringed sideroblasts are red blood cell precursors that have an abnormal amount of iron accumulated in their mitochondria, which forms a ring around the nucleus. This results in the production of abnormal hemoglobin and impaired oxygen transport.
Sideroblastic anemia can be classified as congenital or acquired. Congenital sideroblastic anemias are caused by genetic defects that affect heme synthesis or mitochondrial function, while acquired sideroblastic anemias are associated with various conditions such as myelodysplastic syndromes, chronic alcoholism, lead toxicity, and certain medications.
Symptoms of sideroblastic anemia may include fatigue, weakness, shortness of breath, and pallor. Diagnosis is typically made through a bone marrow aspiration and biopsy, which can identify the presence of ringed sideroblasts. Treatment depends on the underlying cause but may include iron chelation therapy, vitamin B6 supplementation, or blood transfusions.
Succinic acid, also known as butanedioic acid, is an organic compound with the chemical formula HOOC(CH2)2COOH. It is a white crystalline powder that is soluble in water and has a slightly acerbic taste. In medicine, succinic acid is not used as a treatment for any specific condition. However, it is a naturally occurring substance found in the body and plays a role in the citric acid cycle, which is a key process in energy production within cells. It can also be found in some foods and is used in the manufacturing of various products such as pharmaceuticals, resins, and perfumes.
Mitochondrial ADP/ATP translocases, also known as adenine nucleotide translocators (ANT), are a group of proteins located in the inner mitochondrial membrane that play a crucial role in cellular energy production. These translocases facilitate the exchange of adenosine diphosphate (ADP) and adenosine triphosphate (ATP) across the mitochondrial membrane, which is essential for oxidative phosphorylation and thus, energy homeostasis in the cell.
In more detail, during oxidative phosphorylation, ATP is produced within the mitochondria as a result of the electron transport chain's activity. This ATP must be exported to the cytosol for use by the cell's various processes. Simultaneously, the mitochondria need a continuous supply of ADP to sustain the production of ATP. The mitochondrial ADP/ATP translocases facilitate this exchange, allowing for the import of ADP into the mitochondria and the export of ATP to the cytosol.
There are multiple isoforms of the ADP/ATP translocase in humans (ANT1, ANT2, ANT3, and ANT4), encoded by different genes, with varying tissue distributions and functions. Dysfunction of these translocases has been implicated in several pathological conditions, including neurodegenerative diseases, ischemia-reperfusion injury, and cancer.
DNA Mutational Analysis is a laboratory test used to identify genetic variations or changes (mutations) in the DNA sequence of a gene. This type of analysis can be used to diagnose genetic disorders, predict the risk of developing certain diseases, determine the most effective treatment for cancer, or assess the likelihood of passing on an inherited condition to offspring.
The test involves extracting DNA from a patient's sample (such as blood, saliva, or tissue), amplifying specific regions of interest using polymerase chain reaction (PCR), and then sequencing those regions to determine the precise order of nucleotide bases in the DNA molecule. The resulting sequence is then compared to reference sequences to identify any variations or mutations that may be present.
DNA Mutational Analysis can detect a wide range of genetic changes, including single-nucleotide polymorphisms (SNPs), insertions, deletions, duplications, and rearrangements. The test is often used in conjunction with other diagnostic tests and clinical evaluations to provide a comprehensive assessment of a patient's genetic profile.
It is important to note that not all mutations are pathogenic or associated with disease, and the interpretation of DNA Mutational Analysis results requires careful consideration of the patient's medical history, family history, and other relevant factors.
Skeletal muscle, also known as striated or voluntary muscle, is a type of muscle that is attached to bones by tendons or aponeuroses and functions to produce movements and support the posture of the body. It is composed of long, multinucleated fibers that are arranged in parallel bundles and are characterized by alternating light and dark bands, giving them a striped appearance under a microscope. Skeletal muscle is under voluntary control, meaning that it is consciously activated through signals from the nervous system. It is responsible for activities such as walking, running, jumping, and lifting objects.
A missense mutation is a type of point mutation in which a single nucleotide change results in the substitution of a different amino acid in the protein that is encoded by the affected gene. This occurs when the altered codon (a sequence of three nucleotides that corresponds to a specific amino acid) specifies a different amino acid than the original one. The function and/or stability of the resulting protein may be affected, depending on the type and location of the missense mutation. Missense mutations can have various effects, ranging from benign to severe, depending on the importance of the changed amino acid for the protein's structure or function.
Rotenone is not strictly a medical term, but it is a pesticide that is used in some medical situations. According to the National Pesticide Information Center, rotenone is a pesticide derived from the roots and stems of several plants, including Derris Eliptica, Lonchocarpus utilis, and Tephrosia vogelii. It is used as a pesticide to control insects, mites, and fish in both agricultural and residential settings.
In medical contexts, rotenone has been studied for its potential effects on human health, particularly in relation to Parkinson's disease. Some research suggests that exposure to rotenone may increase the risk of developing Parkinson's disease, although more studies are needed to confirm this link. Rotenone works by inhibiting the mitochondria in cells, which can lead to cell death and neurodegeneration.
It is important to note that rotenone is highly toxic and should be handled with care. It can cause skin and eye irritation, respiratory problems, and gastrointestinal symptoms if ingested or inhaled. Therefore, it is recommended to use personal protective equipment when handling rotenone and to follow all label instructions carefully.
I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.
Deafness is a hearing loss that is so severe that it results in significant difficulty in understanding or comprehending speech, even when using hearing aids. It can be congenital (present at birth) or acquired later in life due to various causes such as disease, injury, infection, exposure to loud noises, or aging. Deafness can range from mild to profound and may affect one ear (unilateral) or both ears (bilateral). In some cases, deafness may be accompanied by tinnitus, which is the perception of ringing or other sounds in the ears.
Deaf individuals often use American Sign Language (ASL) or other forms of sign language to communicate. Some people with less severe hearing loss may benefit from hearing aids, cochlear implants, or other assistive listening devices. Deafness can have significant social, educational, and vocational implications, and early intervention and appropriate support services are critical for optimal development and outcomes.
Nervous system diseases, also known as neurological disorders, refer to a group of conditions that affect the nervous system, which includes the brain, spinal cord, nerves, and muscles. These diseases can affect various functions of the body, such as movement, sensation, cognition, and behavior. They can be caused by genetics, infections, injuries, degeneration, or tumors. Examples of nervous system diseases include Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, migraine, stroke, and neuroinfections like meningitis and encephalitis. The symptoms and severity of these disorders can vary widely, ranging from mild to severe and debilitating.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
Lactic acid, also known as 2-hydroxypropanoic acid, is a chemical compound that plays a significant role in various biological processes. In the context of medicine and biochemistry, lactic acid is primarily discussed in relation to muscle metabolism and cellular energy production. Here's a medical definition for lactic acid:
Lactic acid (LA): A carboxylic acid with the molecular formula C3H6O3 that plays a crucial role in anaerobic respiration, particularly during strenuous exercise or conditions of reduced oxygen availability. It is formed through the conversion of pyruvate, catalyzed by the enzyme lactate dehydrogenase (LDH), when there is insufficient oxygen to complete the final step of cellular respiration in the Krebs cycle. The accumulation of lactic acid can lead to acidosis and muscle fatigue. Additionally, lactic acid serves as a vital intermediary in various metabolic pathways and is involved in the production of glucose through gluconeogenesis in the liver.
A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.
Molecular diagnostic techniques are a group of laboratory methods used to analyze biological markers in DNA, RNA, and proteins to identify specific health conditions or diseases at the molecular level. These techniques include various methods such as polymerase chain reaction (PCR), DNA sequencing, gene expression analysis, fluorescence in situ hybridization (FISH), and mass spectrometry.
Molecular diagnostic techniques are used to detect genetic mutations, chromosomal abnormalities, viral and bacterial infections, and other molecular changes associated with various diseases, including cancer, genetic disorders, infectious diseases, and neurological disorders. These techniques provide valuable information for disease diagnosis, prognosis, treatment planning, and monitoring of treatment response.
Compared to traditional diagnostic methods, molecular diagnostic techniques offer several advantages, such as higher sensitivity, specificity, and speed. They can detect small amounts of genetic material or proteins, even in early stages of the disease, and provide accurate results with a lower risk of false positives or negatives. Additionally, molecular diagnostic techniques can be automated, standardized, and performed in high-throughput formats, making them suitable for large-scale screening and research applications.
A sequence deletion in a genetic context refers to the removal or absence of one or more nucleotides (the building blocks of DNA or RNA) from a specific region in a DNA or RNA molecule. This type of mutation can lead to the loss of genetic information, potentially resulting in changes in the function or expression of a gene. If the deletion involves a critical portion of the gene, it can cause diseases, depending on the role of that gene in the body. The size of the deleted sequence can vary, ranging from a single nucleotide to a large segment of DNA.
DNA Sequence Analysis is the systematic determination of the order of nucleotides in a DNA molecule. It is a critical component of modern molecular biology, genetics, and genetic engineering. The process involves determining the exact order of the four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - in a DNA molecule or fragment. This information is used in various applications such as identifying gene mutations, studying evolutionary relationships, developing molecular markers for breeding, and diagnosing genetic diseases.
The process of DNA Sequence Analysis typically involves several steps, including DNA extraction, PCR amplification (if necessary), purification, sequencing reaction, and electrophoresis. The resulting data is then analyzed using specialized software to determine the exact sequence of nucleotides.
In recent years, high-throughput DNA sequencing technologies have revolutionized the field of genomics, enabling the rapid and cost-effective sequencing of entire genomes. This has led to an explosion of genomic data and new insights into the genetic basis of many diseases and traits.
A homozygote is an individual who has inherited the same allele (version of a gene) from both parents and therefore possesses two identical copies of that allele at a specific genetic locus. This can result in either having two dominant alleles (homozygous dominant) or two recessive alleles (homozygous recessive). In contrast, a heterozygote has inherited different alleles from each parent for a particular gene.
The term "homozygote" is used in genetics to describe the genetic makeup of an individual at a specific locus on their chromosomes. Homozygosity can play a significant role in determining an individual's phenotype (observable traits), as having two identical alleles can strengthen the expression of certain characteristics compared to having just one dominant and one recessive allele.
I'm happy to help! However, it seems like there are two terms combined into one request: "Mitochondria" and "Heart." I will provide separate definitions for each.
Mitochondrion (singular) or Mitochondria (plural): These are specialized structures found in the cytoplasm of most eukaryotic cells (cells with a true nucleus), including human cells. They are often referred to as the "powerhouse" of the cell because they generate energy in the form of ATP (adenosine triphosphate) through a process called oxidative phosphorylation. Mitochondria contain their own DNA, which is distinct from the nuclear DNA, and are believed to have originated from ancient bacteria that established a symbiotic relationship with primitive eukaryotic cells.
Heart: In human anatomy, the heart is a muscular organ responsible for pumping blood throughout the body. It is located in the thoracic cavity, slightly left of the center, and is enclosed by the pericardium, a double-walled sac that provides protection and lubrication for the heart's movement. The human heart is divided into four chambers: two atria on the top and two ventricles on the bottom. The right side of the heart receives deoxygenated blood from the body and pumps it to the lungs, while the left side receives oxygenated blood from the lungs and pumps it to the rest of the body. The heart's pumping action is regulated by electrical signals that originate in a group of specialized cardiac muscle cells called the sinoatrial node (SA node).
Fibroblasts are specialized cells that play a critical role in the body's immune response and wound healing process. They are responsible for producing and maintaining the extracellular matrix (ECM), which is the non-cellular component present within all tissues and organs, providing structural support and biochemical signals for surrounding cells.
Fibroblasts produce various ECM proteins such as collagens, elastin, fibronectin, and laminins, forming a complex network of fibers that give tissues their strength and flexibility. They also help in the regulation of tissue homeostasis by controlling the turnover of ECM components through the process of remodeling.
In response to injury or infection, fibroblasts become activated and start to proliferate rapidly, migrating towards the site of damage. Here, they participate in the inflammatory response, releasing cytokines and chemokines that attract immune cells to the area. Additionally, they deposit new ECM components to help repair the damaged tissue and restore its functionality.
Dysregulation of fibroblast activity has been implicated in several pathological conditions, including fibrosis (excessive scarring), cancer (where they can contribute to tumor growth and progression), and autoimmune diseases (such as rheumatoid arthritis).
Reactive Oxygen Species (ROS) are highly reactive molecules containing oxygen, including peroxides, superoxide, hydroxyl radical, and singlet oxygen. They are naturally produced as byproducts of normal cellular metabolism in the mitochondria, and can also be generated by external sources such as ionizing radiation, tobacco smoke, and air pollutants. At low or moderate concentrations, ROS play important roles in cell signaling and homeostasis, but at high concentrations, they can cause significant damage to cell structures, including lipids, proteins, and DNA, leading to oxidative stress and potential cell death.
Cardiomyopathies are a group of diseases that affect the heart muscle, leading to mechanical and/or electrical dysfunction. The American Heart Association (AHA) defines cardiomyopathies as "a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not always) exhibit inappropriate ventricular hypertrophy or dilatation and frequently lead to heart failure."
There are several types of cardiomyopathies, including:
1. Dilated cardiomyopathy (DCM): This is the most common type of cardiomyopathy, characterized by an enlarged left ventricle and impaired systolic function, leading to heart failure.
2. Hypertrophic cardiomyopathy (HCM): In this type, there is abnormal thickening of the heart muscle, particularly in the septum between the two ventricles, which can obstruct blood flow and increase the risk of arrhythmias.
3. Restrictive cardiomyopathy (RCM): This is a rare form of cardiomyopathy characterized by stiffness of the heart muscle, impaired relaxation, and diastolic dysfunction, leading to reduced filling of the ventricles and heart failure.
4. Arrhythmogenic right ventricular cardiomyopathy (ARVC): In this type, there is replacement of the normal heart muscle with fatty or fibrous tissue, primarily affecting the right ventricle, which can lead to arrhythmias and sudden cardiac death.
5. Unclassified cardiomyopathies: These are conditions that do not fit into any of the above categories but still significantly affect the heart muscle and function.
Cardiomyopathies can be caused by genetic factors, acquired conditions (e.g., infections, toxins, or autoimmune disorders), or a combination of both. The diagnosis typically involves a comprehensive evaluation, including medical history, physical examination, electrocardiogram (ECG), echocardiography, cardiac magnetic resonance imaging (MRI), and sometimes genetic testing. Treatment depends on the type and severity of the condition but may include medications, lifestyle modifications, implantable devices, or even heart transplantation in severe cases.
The brain is the central organ of the nervous system, responsible for receiving and processing sensory information, regulating vital functions, and controlling behavior, movement, and cognition. It is divided into several distinct regions, each with specific functions:
1. Cerebrum: The largest part of the brain, responsible for higher cognitive functions such as thinking, learning, memory, language, and perception. It is divided into two hemispheres, each controlling the opposite side of the body.
2. Cerebellum: Located at the back of the brain, it is responsible for coordinating muscle movements, maintaining balance, and fine-tuning motor skills.
3. Brainstem: Connects the cerebrum and cerebellum to the spinal cord, controlling vital functions such as breathing, heart rate, and blood pressure. It also serves as a relay center for sensory information and motor commands between the brain and the rest of the body.
4. Diencephalon: A region that includes the thalamus (a major sensory relay station) and hypothalamus (regulates hormones, temperature, hunger, thirst, and sleep).
5. Limbic system: A group of structures involved in emotional processing, memory formation, and motivation, including the hippocampus, amygdala, and cingulate gyrus.
The brain is composed of billions of interconnected neurons that communicate through electrical and chemical signals. It is protected by the skull and surrounded by three layers of membranes called meninges, as well as cerebrospinal fluid that provides cushioning and nutrients.
Mitochondrial disease
Mitochondrial optic neuropathies
Mitochondrial DNA depletion syndrome
Mitochondrial replacement therapy
Mitochondrial ribosome
Elamipretide
Mitochondrial complex II deficiency
RRM2B
Extrachromosomal DNA
Aleksandra Filipovska
Neurosurgery
Homoplasmy
Genocopy
Melatonin
Neuroacanthocytosis
Threshold expression
Cardiovascular disease in women
Basal ganglia disease
Amyloid-beta precursor protein
Leigh syndrome
Nick Lane
Non-coding RNA
Make a Film Foundation
Mitochondrial carrier
Mitochondrial myopathy
Carolyn Sue
Steve Pieczenik
Dehydrogenase
Boston Children's Hospital
Allen Barnett
Douglass Turnbull
Thymidine phosphorylase
Mitochondrial disease - Wikipedia
Mitochondrial Diseases: MedlinePlus
Mitochondrial disease research makes progress | Fox News
Mitochondrial Dysfunction and Alzheimer's Disease
mitochondrial metabolism disease | SGD
Courtagen, Astellas Partner on Mitochondrial Disease Drug Development | GenomeWeb
Low 'penetrance' of phylogenetic knowledge in mitochondrial disease studies
Mitochondrial DNA and Parkinson disease. Methodologic review]
Genes Mutated in Parkinson's Disease Linked to Mitochondrial Recycling in Neurons
Mitochondrial Disease-The Energy Disease-Remains Mysterious
Mitochondrial Disease Resources | Children's Hospital of Philadelphia
Research | Mitochondrial homeostasis in development, disease & repair | University of Helsinki
What is Mitochondrial Disease? | Children's Hospital of Philadelphia
Estrogen-related receptor gamma regulates mitochondrial and synaptic genes and modulates vulnerability to synucleinopathy | npj...
Frontiers | Mitochondrial Transfer in Cardiovascular Disease: From Mechanisms to Therapeutic Implications
JCI - Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines
Muraresku, McCormick Research Mitochondrial Disease Treatment | Arcadia University
Is Mitochondrial Disease (Mito) Causing Your Health Issues?
More Biomarker Developments: New Blood Biomarker Measures Mitochondrial Damage in Parkinson's | Parkinson's Disease
C. elegans models for human mitochondrial-associated diseases (HMAD) ǀ UKD
New mitochondrial research may ultimately offer hope to those suffering serious disease | Queen's Gazette | Queen's University
Programs & Support<...
Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson's...
Study sheds light on a mitochondrial disease
Table 1 - Mitochondrial Junction Region as Genotyping Marker for Cyclospora cayetanensis - Volume 25, Number 7-July 2019 -...
PTC743 for Treatment of Mitochondrial Disease With Associated Epilepsy
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. |...
Combinatorial screens to identify novel targets to combat mitochondrial diseases. | IRB Barcelona
Mitochondrial dysfunction and neurodegenerative disease | BMG LABTECH
Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer's Disease Brain Is Associated...
Disorders40
- Mitochondrial diseases are a group of metabolic disorders. (medlineplus.gov)
- Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. (wikipedia.org)
- Mitochondrial disorders may be caused by mutations (acquired or inherited), in mitochondrial DNA (mtDNA), or in nuclear genes that code for mitochondrial components. (wikipedia.org)
- This means that mitochondrial DNA disorders may occur spontaneously and relatively often. (wikipedia.org)
- Experiments to treat mitochondrial disorders with traditional gene therapy-swapping defective genes with healthy ones-for example, have borne no fruit. (foxnews.com)
- Mitochondrial disease is a class of rare genetic disorders caused when cellular mitochondria do not properly produce energy. (genomeweb.com)
- There is considerable overlap in the symptoms of many neurological and mitochondrial disorders, making a precise diagnosis difficult," Michael Catalano, senior director of marketing at Courtagen, told GenomeWeb in an email. (genomeweb.com)
- The United Mitochondrial Disease Foundation promotes research for and education about mitochondrial disorders to those affected by them. (chop.edu)
- These include neurodegeneration (Parkinson's disease, ALS), ageing, immune dysfunction, certain forms of cancer and inherited mitochondrial disorders . (helsinki.fi)
- However, we do know that there are many genetic disorders that directly disrupt mitochondrial function. (chop.edu)
- We also discussed the advantage and challenges of mitochondrial transfer strategies, including cell-based mitochondrial transplantation, extracellular vesicle-based mitochondrial transplantation, and naked mitochondrial transplantation, for the treatment of cardiovascular disorders. (frontiersin.org)
- Muraresku and McCormick, who returned to Arcadia to teach Biochemical Genetics, are dedicated to helping students get firsthand experience in genetics, mitochondrial disorders, and metabolic disorders. (arcadia.edu)
- Therefore, mitochondrial malfunction can lead to a broad gamut of disorders. (holtorfmed.com)
- Part of the reason that mitochondrial disorders present so many varied symptoms is because it is highly integrated with most of the body. (holtorfmed.com)
- Maglioni S, Ventura N. (2016) C. elegans as a model organism for human mitochondrial associated disorders. (uniklinik-duesseldorf.de)
- Despite major advances in our understanding of the pathophysiology of mitochondrial diseases, we have no cures for these disorders. (irbbarcelona.org)
- To address this need, I have employed a combination of chemical and CRISPR/Cas9 genome-editing screenings to identity novel genes and molecular targets that can be exploited therapeutically to treat mitochondrial disorders.Loss-of-function screens yielded BRD4 protein as a molecular target. (irbbarcelona.org)
- BRD4 inhibition, either chemically or genetically, remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by inhibition of Complex I. Conversely, gain-of-function screens identified a previously uncharacterized link between electron transport chain functional and cellular redox homeostasis with relevant implications in neurodegenerative disorders associated with mitochondrial dysfunction. (irbbarcelona.org)
- Dr. Matthew B. Klein, MD, MS, FACS is Chief Development Officer at PTC Therapeutics, Inc. Prior to joining PTC, Dr. Klein was CEO and Chief Medical Officer of BioElectron Technology Corporation, a biotechnology company focused on development of redox active small molecules for mitochondrial disease and related disorders of oxidative stress. (mitoaction.org)
- Many factors can contribute to mitochondrial dysfunction including genetic mutations, aging, environmental factors, nutritional deficiencies, and metabolic disorders. (bmglabtech.com)
- In close collaboration with our partner NeuroVive, we have a great possibility to develop KL1333 into a novel treatment opportunity for patients with genetic mitochondrial disorders, such as MELAS," said Soo-Hyun Lew, M.D. Executive Director of Development at Yungjin Pharm. (cision.com)
- The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. (cision.com)
- It is in clinical development stage intended to document the use for chronic oral treatment in primary genetic mitochondrial disorders such as MELAS, KSS, CPEO, PEO, Pearson and MERRF. (cision.com)
- Its mode of action is complementary to that of NVP015, which is intended to alleviate acute episodes of energy crises in genetic mitochondrial disorders with dysfunction in complex I and to NVP025, intended to protect the mitochondria in skeletal muscle from dysfunctional calcium handling and consequential muscle wasting. (cision.com)
- The Lily Foundation, the UK's leading mitochondrial disease charity, says that a "substantial number of children with mitochondrial disorders do not reach adulthood. (mdlinx.com)
- An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. (centrodinoferrari.com)
- While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. (centrodinoferrari.com)
- We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion. (centrodinoferrari.com)
- The doctoral study found that mitochondrial diseases, together with ion channel diseases, chromosomal disorders and neurocutaneous syndromes, are a relatively common genetic cause of prolonged epileptic seizures, i.e. status epilepticus. (oulu.fi)
- The role of liver transplantation in the treatment of acute liver injury in patients with mitochondrial disorders has been controversial due to the progressive nature of the underlying disease. (oulu.fi)
- Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. (infertile.com)
- Q: What are mitochondrial diseases or disorders? (cdc.gov)
- Mitochondrial diseases and disorders are the same thing. (cdc.gov)
- When a child has both autism and a mitochondrial disease, they sometimes have other problems as well, including epilepsy, problems with muscle tone, and/or movement disorders. (cdc.gov)
- Huntington disease (HD) is a genetic, autosomal dominant, neurodegenerative disorder characterized clinically by disorders of movement, progressive dementia, and psychiatric and/or behavioral disturbance. (medscape.com)
- Mitochondrial disorders are frequently associated with seizures. (medscape.com)
- Mitochondrial disorders cause mitochondria to stop working properly, so that less and less energy is generated within the cells. (msdmanuals.com)
- These high-energy organs are particularly susceptible to the problems caused by mitochondrial disorders. (msdmanuals.com)
- The following are examples of mitochondrial disorders. (msdmanuals.com)
- At that time, the differentiation between the spinal muscular atrophies and weakness associated with central nervous system disorders and primary muscle disease had not been established. (medscape.com)
Parkinson's28
- Parkinson's disease (PD), a disorder of unknown etiology, is associated with the degeneration of dopaminergic neurons in nigro-striatal pathways. (nih.gov)
- Studies headed by researchers at the Gladstone Institutes have generated new insights into the role played by genes known as PINK1 and Parkin, which are associated with Parkinson's disease, in the recycling of energy-generating mitochondria in brain cells. (genengnews.com)
- This work gives us unprecedented insight into mitochondria's life cycle and how they are recycled by key proteins that, when mutated, cause Parkinson's disease," Nakamura commented. (genengnews.com)
- Mutations in these same proteins also cause hereditary forms of Parkinson's disease. (genengnews.com)
- While the role of PINK1 and Parkin in mitophagy has been heavily studied in many cell types, it has been unclear whether these proteins act the same way in neurons, which are also the cells that die in Parkinson's disease. (genengnews.com)
- Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons," the investigators noted. (genengnews.com)
- The high resolution of the approach should help researchers gain a more detailed understanding of how Parkin and PINK1 affect mitochondrial degradation in Parkinson's disease. (genengnews.com)
- Gladstone researchers, including Ken Nakamura (left), Zak Doric (center), and Huihui Li (right), tracked mitochondria inside neurons and uncovered a new recycling pathway that may be linked to Parkinson's disease. (genengnews.com)
- We're also working to identify connections between mitochondrial disease and other conditions like Alzheimer's disease, Parkinson's disease, diabetes, aging, and cancer. (chop.edu)
- Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc) and the development of alpha-synuclein-containing aggregates called Lewy-bodies and Lewy-neurites 1 . (nature.com)
- For example, those with chronic conditions such as Lou Gehrig's disease (ALS), Chronic Fatigue Syndrome, and Parkinson's may have developed them because of dysfunctional mitochondria. (holtorfmed.com)
- In a breakthrough earlier this year, researchers validated the first test that can detect Parkinson's disease (PD) biology in living people. (michaeljfox.org)
- Called the α-synuclein seeding amplification assay (αSyn-SAA), the test uses spinal fluid to reveal a key biomarker of the disease - abnormal alpha-synuclein - in people diagnosed with Parkinson's as well as people at a high risk of developing it but who have not yet shown symptoms. (michaeljfox.org)
- The new biomarker is similar to αSyn-SAA in diagnosing PD objectively based on biology, but mitochondrial DNA and alpha-synuclein tests measure different aspects of Parkinson's. (michaeljfox.org)
- There's tremendous innovation in tests to diagnose Parkinson's disease better and earlier, and it's happening rapidly," Frasier said. (michaeljfox.org)
- The discovery of new biomarkers sits on the leading edge of a new biology-based era in Parkinson's disease, one that includes earlier detection of the disease and the promise of better therapies for slowing or stopping its progression at any point in the disease process. (michaeljfox.org)
- Mitochondrial degeneration is considered one of the major causes of Parkinson's disease (PD). (nature.com)
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of midbrain DA neurons. (nature.com)
- Defects in mitophagy have been linked to neurodegenerative ailments such as Parkinson's and Alzheimer's disease and many other pathophysiological conditions. (medicalxpress.com)
- The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. (alzforum.org)
- Canet-Avilés RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR . The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization . (alzforum.org)
- The disruption of mitochondrial function is a known contributor to neurodegenerative diseases like Parkinson's and Alzheimer's disease, although the precise details remain to be worked out. (bmglabtech.com)
- In Parkinson's disease, a strong link between mitochondrial dysfunction and disease-associated genes has been documented. (bmglabtech.com)
- Mutations in the PINK1 gene (also known as PARK6) are associated with early onset Parkinson's disease. (bmglabtech.com)
- Cardiolipin as a biomarker of mitochondrial dysfunction associated with Parkinson's disease. (cdc.gov)
- A New Clue Into the Cause, Spread of Parkinson's Disease? (medscape.com)
- Damaged mitochondrial DNA (mtDNA) initiates and spreads Parkinson's disease (PD) pathology, potentially opening new avenues for early diagnosis, disease monitoring, and drug development. (medscape.com)
- S donor with mitochondrial targeting function for treatment of Parkinson's disease. (bvsalud.org)
MtDNA17
- Mitochondrial DNA, however, is inherited from the mother only (with some exceptions) and each mitochondrion typically contains between 2 and 10 mtDNA copies. (wikipedia.org)
- If only a few of the mtDNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria (for more detailed inheritance patterns, see human mitochondrial genetics). (wikipedia.org)
- This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as the basis for Alzheimer's disease. (scirp.org)
- An up-to-date view of the worldwide mitochondrial DNA (mtDNA) phylogeny together with an evaluation of the conservation of each site is a reliable tool for detecting errors in mtDNA studies and assessing the functional importance of alleged pathogenic mutations. (nih.gov)
- Thirty-eight of the 69 articles were either reviews about mitochondrial diseases (19 articles) or original articles not related to mtDNA (19 articles). (nih.gov)
- These structures can damage mitochondria and mitochondrial DNA (mtDNA). (holtorfmed.com)
- Mitochondrial diseases are caused by mutations to mitochondrial DNA (mtDNA) gene or a mutation in a nuclear gene (nDNA). (mdlinx.com)
- There are many kinds of mitochondrial diseases, and more than 250 pathogenic mutations to mtDNA have been reported. (mdlinx.com)
- The cohort will also allow definitive studies on the transmission of mtDNA mutations, and provide longitudinal data on the natural history of the disease. (bmj.com)
- Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multisystem disease. (jci.org)
- The wide range of manifestations observed in patients with mitochondrial disease results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. (jci.org)
- Here, we identify nonrandom distribution of a pathogenic mtDNA variant across a complex tissue using single-cell RNA-Seq, mitochondrial single-cell ATAC sequencing, and multimodal single-cell sequencing. (jci.org)
- Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. (infertile.com)
- Here, we summarize how the m.3243G mtDNA mutation affects mitochondrial function in different tissues using iPSC and iPSC-differentiated cell type disease models and what significant findings have been replicated in the independent studies. (bvsalud.org)
- This has direct implication for clinical diagnosis" ― if damaged mtDNA can be detected in blood, it could serve as an early biomarker for disease, she explained. (medscape.com)
- In the current study, using postmortem brain tissue samples from patients with sporadic PD, they confirmed that that there were deletions of mtDNA in the medial frontal gyrus, a region implicated in cognitive impairments in PD, suggesting a potential role of damaged mtDNA in disease pathophysiology. (medscape.com)
- Looking ahead, they plan to investigate how mtDNA damage can serve as a predictive marker for different disease stages and progression and to explore potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in PD. (medscape.com)
Alzheimer's15
- Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of basal forebrain cholinergic neurons, leading to reduction in transmission through cholinergic fibers involved in processes of attention, learning, and memory. (scirp.org)
- This review focuses on the evidence supporting a clear association between amyloid- β toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer's disease. (scirp.org)
- To date, the beta amyloid (A β ) cascade hypothesis still remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is uncertain. (scirp.org)
- F. Albrekkan and M. Kelly-Worden, "Mitochondrial Dysfunction and Alzheimer's Disease," Open Journal of Endocrine and Metabolic Diseases , Vol. 3 No. 2A, 2013, pp. 14-19. (scirp.org)
- C. Supnet and I. Bezprozvanny, "Presenilins as Endoplasmic Reticulum Calcium Leak Channels and Alzheimer's Disease Pathogenesis," Science China Life Sciences, Vol. 54, No. 8, 2011, pp. 744-751. (scirp.org)
- P. A. Trimmer and M. K. Borland, "Differentiated Alzheimer's Disease Transmitochondrial Cybrid Cell Lines Exhibit Reduced Organelle Movements," Antioxid Redox Signaling, Vol. 7, No. 9-10, 2005, pp. 1101-1109. (scirp.org)
- M. Dumont, M. T. Lin and M. F. Beal, "Mitochondria and Antioxidant Targeted Therapeutic Strategies for Alzheimer's Disease," Journal of Alzheimer's Disease, Vol. 20, 2010, pp. 633-643. (scirp.org)
- Mitochondrial dysfunction is one of the major intracellular lesions of Alzheimer's disease (AD). (jneurosci.org)
- Several lines of evidence suggest the involvement of mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
- In addition to less ATP production and higher levels of reactive oxygen species, mitochondria in the brains of individuals with Alzheimer's disease show mitochondrial abnormalities that include altered shape, decreased density, and impaired respiration. (bmglabtech.com)
- Evidence also points to multiple genes being linked to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
- In this context, studies using positron emission tomography have indicated decreased use of glucose and impaired oxidative metabolism in the brains of patients with Alzheimer's disease. (bmglabtech.com)
- Altered mitochondrial dynamics, including excessive fission and fusion of mitochondria, also contribute to mitochondrial dysfunction in Alzheimer's disease. (bmglabtech.com)
- Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). (benthamscience.com)
- The EU Joint Programme - Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular, Alzheimer's. (neurodegenerationresearch.eu)
Children's Hospital of3
- This presentation was developed by the mitochondrial medicine team at Children's Hospital of Philadelphia. (chop.edu)
- The first mitochondrial DNA disease was only discovered in 1988 by Dr. Doug Wallace, who is now here at Children's Hospital of Philadelphia. (chop.edu)
- Genetic Counseling alumnae Colleen Muraresku '09, '11M and Elizabeth McCormick '09, '11M , genetic counselors and researchers for the Children's Hospital of Philadelphia (CHOP)'s Mitochondrial Medicine Frontier program, published "Mitochondrial Disease: Advances in Clinical Diagnosis, Management, Therapeutic Development, and Preventative Strategies" in Current Genetic Medicine Reports . (arcadia.edu)
United Mitochondrial Disease Foundation1
- They include MitoAction, https://www.mitoaction.org , and the United Mitochondrial Disease Foundation, https://www.umdf.org . (allsup.com)
Patients with mitochondrial disease3
- 15 clinical studies have been approved by MDOC, involving over 250 patients with mitochondrial disease. (bmj.com)
- Conclusion For the first time in the UK it is possible to access a large cohort of well-characterised patients with mitochondrial disease. (bmj.com)
- Zoe presents the theory of how KDT works in mitochondrial disease and shares her own experience of managing patients with mitochondrial disease with KDT. (nutricia.co.uk)
Lactic Acidosis4
- We profiled the transcriptome, chromatin accessibility state, and heteroplasmy in cells from the eyes of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and from healthy control donors. (jci.org)
- The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) has strokelike events that are acute in onset, often transient, and occasionally associated with a febrile illness. (medscape.com)
- The prevalence of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) is 16-18/100,000, with the highest reported diagnostic rate in Western regions and the lowest rate in Asia. (medscape.com)
- Human induced pluripotent stem cells (hiPSCs) for MELAS syndrome ( mitochondrial myopathy , encephalopathy , lactic acidosis , stroke -like episodes) may allow deeper understanding of how tissue -specific mitochondrial dysfunction result in multi-systemic disease . (bvsalud.org)
Genetic18
- Genetic mutations cause these diseases. (medlineplus.gov)
- Scientists have made significant advances in the quest to treat mitochondrial disease, an incurable genetic malady that afflicts thousands of U.S. children each year. (foxnews.com)
- When genetic mutations disrupt this process, it can trigger a range of ailments, including deafness, diabetes, heart disease and dementia. (foxnews.com)
- Furthermore, the "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic, and pathological features of sporadic AD. (scirp.org)
- Under the terms of the deal, Courtagen will use its ZiPhyr bioinformatics platform - which analyzes genetic variant data using proprietary algorithms to determine the pathogenicity of mutations and identify potential disease targets - to help Astellas develop a predictive model to test mitochondrial disease drug candidates. (genomeweb.com)
- Genetic based mitochondrial disease is chronic, meaning that its symptoms last over time. (chop.edu)
- At Children's Hospital, mitochondrial medicine patients are cared for by an entire team of experts, including a suite of primary mito docs and diverse specialty physicians, genetic counselors, a nurse practitioner, nurses, a dietician, a social worker, patient navigators, physical therapists and an exercise physiologist. (chop.edu)
- We are characterizing mitochondrial and neuronal deficits in these models through a combination of behavioral, genetic and biochemical assays. (uniklinik-duesseldorf.de)
- NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine, with one project in clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project in clinical phase I (KL1333) for genetic mitochondrial diseases. (cision.com)
- The study investigated the genetic causes of status epilepticus using patient data collected from four university hospitals, focusing on the genetic alterations in mitochondrial and nuclear genes involved in mitochondrial disease and epilepsy. (oulu.fi)
- In addition, certain common non-disease-causing genetic variants previously associated with an increased risk of liver injury during valproate treatment were studied. (oulu.fi)
- Moreover, mitochondrial genetic alterations are estimated to affect up to 1/200 people worldwide, most of whom are healthy carriers. (oulu.fi)
- Early identification of individuals with mitochondrial disease and related epilepsy and of the underlying genetic causes is important not only for patient and family counselling but also for individual patient care planning. (oulu.fi)
- The increasing use of genetic research in the diagnosis of epilepsy is likely to be reflected not only in the increasing recognition of mitochondrial diseases but also in the understanding of the underlying disease mechanisms and, consequently, of the mechanisms of adverse drug actions on mitochondria. (oulu.fi)
- They reviewed clinical and genetic features in 34 cases of late-onset Huntington disease. (medscape.com)
- Accordingly, epilepsy in mitochondrial disease straddles the genetic and structural/metabolic categories in the 2010 International League Against Epilepsy (ILAE) classification of the epilepsies outlined in Table 1 . (medscape.com)
- A large driver for the restructuring of this classification is the ongoing advance in genetic medicine and diagnostic technologies, [ 13 ] exemplified by increasing descriptions of epilepsy causing gene variations [ 14 ] and mirrored in the field of mitochondrial disease. (medscape.com)
- [ 15 ] As a combined consequence of the phenotypic diversity, the increasing genetic complexity and a historical paucity of detailed seizure semiology, the clinician is faced with a considerable challenge in identifying, classifying, and treating epilepsy arising due to mitochondrial disease. (medscape.com)
Mutations in mitochondrial1
- In addition, mutations in mitochondrial DNA have been associated with an increased risk of the disease. (bmglabtech.com)
Role of mitochondrial3
- Researchers, however, are planning future studies to validate and improve the blood test and learn more about the role of mitochondrial DNA damage in PD. (michaeljfox.org)
- Generally un-related patients are used to study role of mitochondrial SNP on human disease. (biostars.org)
- The role of mitochondrial dysfunction in HD has been under investigation. (medscape.com)
Centers for Diseas3
- Centers for Disease Control and Prevention. (cdc.gov)
- The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. (cdc.gov)
- The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website. (cdc.gov)
Genetics4
- her type of mitochondrial disease linked back to genetics. (allsup.com)
- Jaya Ganesh, MD, an associate professor at the Department of Genetics and Genomic Sciences and director of the Mitochondrial Diseases program at the Icahn School of Medicine at Mount Sinai, explains that mitochondrial diseases affect the mitochondria, which are "the subcellular organelles important for energy production, ATP synthesis…and other functions, like regulating calcium, regulating the aging process, and managing certain reactive oxygen species. (mdlinx.com)
- Knowledge and experience in evaluating mitochondrial function and/or mitochondrial genetics. (ibecbarcelona.eu)
- Advances in molecular genetics have help in the discovery of significant information on the relationship between muscle biology and clinical neuromuscular diseases. (medscape.com)
Neuronal6
- Nakamura is senior author of the researchers' published paper in Science Advances , which is titled, " Longitudinal tracking of neuronal mitochondria delineates PINK1/Parkin-dependent mechanisms of mitochondrial recycling and degradation . (genengnews.com)
- Mitochondrial accumulation of APP was also observed in the cholinergic, dopaminergic, GABAergic, and glutamatergic neuronal types in the category III AD brains. (jneurosci.org)
- This can impair processes like mitochondrial transport and the clearance of proteins leading to bioenergetic deficits and neuronal dysfunction. (bmglabtech.com)
- 4 Interestingly, Cdk5 has been shown to act as a mitochondrial regulator during neuronal apoptosis. (bmj.com)
- Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. (bmj.com)
- In mice PD models that were deficient in IFNβ signaling, the investigators showed that neuronal IFNβ is required to maintain mitochondrial homeostasis and metabolism. (medscape.com)
Disorder9
- the mutation that in one individual may cause liver disease might in another person cause a brain disorder. (wikipedia.org)
- An inherited metabolic disorder that involves mitochondrial metabolism dysfunction. (yeastgenome.org)
- Much like an autoimmune disorder, mitochondrial dysfunction can exhibit symptoms associated with numerous conditions. (holtorfmed.com)
- It depends on the type of mitochondrial disorder. (umdf.org)
- A mitochondrial disorder featuring the triad of chronic progressive EXTERNAL OPHTHALMOPLEGIA, cardiomyopathy (CARDIOMYOPATHIES) with conduction block (HEART BLOCK), and RETINITIS PIGMENTOSA. (nih.gov)
- More research is needed to find out how common it is for people to have autism and a mitochondrial disorder. (cdc.gov)
- Encephalopathy is a medical term for a disease or disorder of the brain. (cdc.gov)
- Regressive encephalopathy means there is a disease or disorder in the brain that makes a person lose skills they once had. (cdc.gov)
- This buildup of lactic acid may help distinguish a mitochondrial disorder from other metabolic diseases. (msdmanuals.com)
Nuclear-encoded mitochondrial genes1
- Direct regulators of nuclear-encoded mitochondrial genes are members of the estrogen-related receptor (ERR) family, encoded by Esrra , Esrrb and Esrrg . (nature.com)
Encephalomyopathic mitochondrial DNA depletion1
- Thirumalesh's case echoes that of an infant named Charlie Gard, who died from encephalomyopathic mitochondrial DNA depletion syndrome (MDDS). (mdlinx.com)
Diagnosis2
- Noah's family were referred to Very Special Kids in 2015, shortly after he received the diagnosis of Mitochondrial disease. (vsk.org.au)
- Median survival from diagnosis is approximately 17 years, including a subgroup with severe disease with a much shorter lifespan from diagnosis. (medscape.com)
Outer mitochon4
- Depolarized mitochondria recruit Parkin to the outer mitochondrial membrane, triggering autophagosome formation, rapid lysosomal fusion, and Parkin redistribution," the team noted. (genengnews.com)
- Furthermore, in AD brains, mitochondrially associated APP formed stable ∼480 kDa complexes with the translocase of the outer mitochondrial membrane 40 (TOM40) import channel and a super complex of ∼620 kDa with both mitochondrial TOM40 and the translocase of the inner mitochondrial membrane 23 (TIM23) import channel TIM23 in an "N in mitochondria -C out cytoplasm " orientation. (jneurosci.org)
- The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1) and 2 (MFN2), located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1), in the inner membrane. (centrodinoferrari.com)
- Fusion of the outer mitochondrial membrane depends on two GTPase family members: mitofusin 1 (MFN1) and mitofusin 2 (MFN2). (centrodinoferrari.com)
Oxidative stress and mitochondrial1
- Drosophila CHCHD2 ( dCHCHD2 ) knockout flies exhibit PD-like phenotypes in an age-dependent manner, which include dysfunction in motor ability, DA neuron loss, increased oxidative stress and mitochondrial cristae degeneration 2 . (nature.com)
Clinical10
- Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them. (wikipedia.org)
- However, clinical trials of these agents for cardiovascular diseases were hardly approved to carry out, even less to evaluate their clinical effectiveness and safety. (frontiersin.org)
- If the test is optimized, it could be used in clinical trials to identify drugs that reverse or halt mitochondrial DNA damage and the disease process. (michaeljfox.org)
- In his past positions, Francesco conducted various clinical trials in Alzheimer disease, epilepsy and liver disease, all studies that led to multiple regulatory submissions and approvals with the FDA, EMA and other global regulatory agencies. (mitoaction.org)
- Currently, he is the Vice President of Clinical Development at PTC Therapeutics, where he is the clinical lead of the DMD and mitochondrial epilepsy projects. (mitoaction.org)
- The company's strategy is to advance drugs for rare diseases through clinical development and into the market. (cision.com)
- All patient data is entered anonymously and unique identifiers are used to contact patients suitable for clinical studies.The Mitochondrial Disease Oversight Committee (MDOC), which includes an ethicist and a patient representative, was established to evaluate the scientific merit and appropriateness of applications and govern utilisation of the Cohort. (bmj.com)
- Clinical studies are part of clinical research and at the heart of all medical advances, including rare diseases. (nih.gov)
- Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. (nih.gov)
- Since the symptoms, signs, and acute clinical presentations are so varied and the disease is relatively rare, the disease is misdiagnosed frequently. (medscape.com)
Called mitochondrial dynamics1
- This new field of study is called mitochondrial dynamics and it reveals how abnormalities in the life cycle of mitochondria (including the ways mitochondria divide (fission), join together (fusion) and are eliminated) result in disease causing changes in cell growth and survival. (queensu.ca)
Improve mitochondrial function2
- Several studies suggest that targeting PGC-1α to improve mitochondrial function could be a potential therapeutic strategy. (nature.com)
- Understanding the role of mitochondria in one's health, its link to serious conditions and ways to protect and improve mitochondrial function can help keep one's health at its best. (holtorfmed.com)
Acquired mitochondrial dysfunction1
- They may also be the result of acquired mitochondrial dysfunction due to adverse effects of drugs, infections, or other environmental causes. (wikipedia.org)
Depletion syndrome1
- Sometimes mitophagy can be over-active and patients are left with too few mitochondria for the bodies energy needs and suffer from mitochondrial depletion syndrome. (medicalxpress.com)
Metabolism5
- It is not surprising, therefore that mitochondrial damage and aberrant mitochondrial metabolism are associated with a diverse array of human diseases. (helsinki.fi)
- These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium. (jci.org)
- Progressive mitochondrial accumulation of incompletely translocated APP caused mitochondrial dysfunction and impaired cellular energy metabolism. (jneurosci.org)
- KL1333 has in preclinical models been demonstrated to increase mitochondrial energy output, reduce lactate accumulation, diminish the formation of free radicals, and to have long-term beneficial effects on energy metabolism such as the formation of new mitochondria. (cision.com)
- There are a number of disease states, including Friedreich's ataxia (FA) and sideroblastic anemia, where iron metabolism is dysregulated and leads to mitochondrial iron accumulation. (curefa.org)
Mutation4
- therefore, mutations occur more frequently in mitochondrial DNA than in nuclear DNA (see Mutation rate). (wikipedia.org)
- Most mitochondrial disease is inherited by a person from a gene mutation or change in the mitochondrial DNA or in the nuclear DNA from one or both of their parents. (chop.edu)
- So you would want some estimate of how often a mitochondrial mutation shows up (to do it right, you would need a mutation caller with non-diploid assumptions) and see if prevalence of mutation is associated with disease while keeping in mind that the prevalence should be similar for members with shared maternal ancestry. (biostars.org)
- Mitochondrial DNA is 10 times more prone to mutation than somatic DNA. (medscape.com)
Types of mitochondrial1
- There are multiple types of mitochondrial diseases. (mdlinx.com)
Treatment of mitochondrial2
- The contract will be within the framework of the "Generation of therapies and biomarkers for the treatment of mitochondrial dysfunction driven neurodegenerative diseases" (DRUG4-COXPD1) project prioritized by the IBEC under the "Plan Complementario de Biotecnología aplicada a la Salud" ( biotechnology applied to health ). (ibecbarcelona.eu)
- Before you begin taking any supplements, you should be evaluated by a healthcare provider who is trained in treatment of mitochondrial disease and its management. (integrative-medicine-clinics.com)
Gene6
- We demonstrate that deletion of ERRγ from DAergic neurons in adult mice was sufficient to cause a levodopa-responsive PD-like phenotype with reductions in mitochondrial gene expression and number, that partial deficiency of ERRγ hastens synuclein-mediated toxicity, and that ERRγ overexpression reduces inclusion load and delays synuclein-mediated cell loss. (nature.com)
- The loss of the PD-associated mitochondrial gene CHCHD2 resulted in reduced ATP production, enhanced mitochondrial peroxide production and lower Ca 2+ -buffering activity in dopaminergic (DA) terminals in flies. (nature.com)
- The researcher will work primarily with mouse models of disease, especially in preclinical gene therapy studies applied to these models. (ibecbarcelona.eu)
- Gene expression in a Drosophila model of mitochondrial disease. (cabd.es)
- Huntington disease (HD) is associated with an excessive sequence of CAG repeats in the 5' end of HTT (alias IT15- interesting transcript number 15), a 350-kD gene located on the short arm of chromosome 4. (medscape.com)
- 27 disease terms (MeSH) has been reported with ACADM gene. (cdc.gov)
Relationship between mitochondrial2
- In this blog, we look at the relationship between mitochondrial dysfunction and neurodegenerative disease. (bmglabtech.com)
- Q: Is there a relationship between mitochondrial disease and autism? (cdc.gov)
Fission6
- We combined time-lapse microscopy and correlative light and electron microscopy to track individual mitochondria in neurons lacking the fission-promoting protein dynamin-related protein 1 (Drp1) and delineate the kinetics of PINK1-dependent pathways of mitochondrial quality control," they pointed out. (genengnews.com)
- Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. (centrodinoferrari.com)
- Mitochondrial fusion and fission are fundamental processes underlying cellular dynamics [1]. (centrodinoferrari.com)
- Fission is necessary for proper mitochondrial transport, which depends on the specific energy demands of subcellular regions. (centrodinoferrari.com)
- Dynamin-related protein 1 (DRP1), a cytosolic dynamin-related GTPase, plays a central role in fission by promoting mitochondrial division through its oligomerization into multimeric spiral structures [5]. (centrodinoferrari.com)
- among them, mitochondrial fission 1 and mitochondrial fission factor have been proposed to be involved in DRP1 recruitment, although recent in vitro studies seem to not support this hypothesis [6, 7]. (centrodinoferrari.com)
Pathogenesis6
- Mitochondrial dysfunction is evident in early stages of AD and is involved in AD pathogenesis. (scirp.org)
- Mitochondrial dysfunction has been proven to play a critical role in the pathogenesis of cardiovascular diseases. (frontiersin.org)
- The abnormal morphology and dysfunction of mitochondria have been proven as the principal mechanisms in the pathogenesis of cardiovascular diseases, such as heart failure, myocardial infarction, atherosclerosis, and hypertension ( 4 - 6 ). (frontiersin.org)
- 1,2 The molecular mechanisms underlying striatal vulnerability are still unknown, but growing evidences suggest that mitochondrial dysfunction occurs during the pathogenesis of the disease. (bmj.com)
- Redox stress is associated with the pathogenesis of a wide variety of disease states. (curefa.org)
- Quintanilla et al published the results of a study that focused on the contribution of mitochondrial dysfunction and transcriptional dysregulation to the pathogenesis of HD and the possibility of therapeutic intervention. (medscape.com)
Challenges of mitochondrial1
- Explore our offerings and discover the support you need to navigate the challenges of mitochondrial disease with confidence and resilience. (mitoaction.org)
Proteins5
- Human mitochondrial DNA encodes 13 proteins of the respiratory chain, while most of the estimated 1,500 proteins and components targeted to mitochondria are nuclear-encoded. (wikipedia.org)
- Accumulation of APP across mitochondrial import channels, which varied with the severity of AD, inhibited the entry of nuclear-encoded cytochrome c oxidase subunits IV and Vb proteins, which was associated with decreased cytochrome c oxidase activity and increased levels of H 2 O 2 . (jneurosci.org)
- Considering FA, which is due to the decreased expression of the mitochondrial protein, frataxin, this iron accumulation does not occur within protective storage proteins such as mitochondrial ferritin. (curefa.org)
- He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA. (medscape.com)
- Protein drugs are a critically important therapeutic modality due to the sophisticated binding recognition, catalytic properties, and disease relevance of proteins. (bvsalud.org)
Impairment of mitochondrial2
- Nevertheless, the mechanisms related to the impairment of mitochondrial functions specific to AD remain unclear. (jneurosci.org)
- This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. (centrodinoferrari.com)
Symptoms11
- The symptoms of mitochondrial disease can vary. (medlineplus.gov)
- There are no cures for these diseases, but treatments may help with symptoms and slow down the disease. (medlineplus.gov)
- A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies. (wikipedia.org)
- For most of us, the batteries may not be as full, but there is still plenty of energy to function well, but when mitochondria fail, they produce less and less energy within cells, which can result in a range of acute or chronic disease symptoms. (chop.edu)
- The average mitochondrial disease patient has 16 unique symptoms, which can make diagnosing a common root cause challenging. (chop.edu)
- If one has severe mitochondrial dysfunction they may experience extreme symptoms such as seizures or an inability to get out of bed. (holtorfmed.com)
- What's especially exciting is that the data suggests the mitochondrial changes occur prior to developing symptoms, so the test could be used for early detection," said Mark Frasier, PhD, The Michael J. Fox Foundation (MJFF) chief scientific officer. (michaeljfox.org)
- When Do Symptoms of Renal tubulopathy, diabetes mellitus, and cerebellar ataxia due to duplication of mitochondrial DNA Begin? (nih.gov)
- Mitochondrial disease symptoms can be mild or severe, and the disease tends to affect children most often, but adult onset of the disease is happening more often. (integrative-medicine-clinics.com)
- Not everyone with a mitochondrial disease will show symptoms. (cdc.gov)
- However, when discussing the group of mitochondrial diseases that tend to affect children, symptoms usually appear in the toddler and preschool years. (cdc.gov)
Defects5
- Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases. (wikipedia.org)
- Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations. (wikipedia.org)
- These mitochondrial defects can be widely rescued by Cdk5 inhibition with roscovitine or Cdk5 knockdown with siRNA transfection. (bmj.com)
- Altogether, our findings support the hypothesis that Cdk5 plays a crucial role in mitochondrial defects involved in the striatal neurodegeneration in HD. (bmj.com)
- Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation. (cabd.es)
Encephalopathy1
- Ictal activity in mitochondrial disease may result from metabolic disturbance, encephalopathy, or an acquired structural lesion such as a stroke-like episode. (medscape.com)
Treat mitochondrial1
- Therefore, there is an urgent unmet medical need to develop new technologies and platforms for identifying therapeutic opportunities to treat mitochondrial diseases. (irbbarcelona.org)
Human mitochondrial1
- PON-mt-tRNA is a posterior probability-based tool for classification of human mitochondrial tRNA (mt-tRNA) variations. (lu.se)
Mitochondria fail2
- However, when mitochondria fail to function properly different neurodegenerative diseases can take hold. (bmglabtech.com)
- Mitochondrial disease occurs when mitochondria fail to produce energy, leading to health problems of many kinds. (integrative-medicine-clinics.com)
Homeostasis3
- A primary goal of our research is to both exploit and develop tools to understand mitochondrial homeostasis in health and disease. (helsinki.fi)
- Studies have shown that cell-to-cell mitochondrial transfer plays an essential role in regulating cardiovascular system development and maintaining normal tissue homeostasis under physiological conditions. (frontiersin.org)
- Based on their findings, Quintanilla et al suggest the possibility that the effects of mutant HD can be reduced by increasing the availability and activity of PGC-1 α, a co-activator involved in mitochondrial function and glucose, lipid, and energy homeostasis, the function of which seems to be disrupted by mutant HD interactions that interfere with signaling pathways. (medscape.com)
Mechanisms3
- Consequently, our cells have evolved multiple mechanisms to cope with mitochondrial meltdown. (helsinki.fi)
- A deeper understanding of the mechanisms underlying DAergic neuron susceptibility is needed to generate disease-modifying therapies for PD. (nature.com)
- In Alzheimer s disease (AD) there appear to be changes in mitochondria, although we are unsure of the exact molecular mechanisms driving this. (neurodegenerationresearch.eu)
Genome2
- Because complex I is partially encoded by the mitochondrial genome, several studies have searched for mitochondrial (mt) DNA abnormalities in patients with PD. (nih.gov)
- Recently, scientists have shown that DNA methylation, a key epigenetic mark, also regulates genes in the mitochondrial genome. (neurodegenerationresearch.eu)
Neurodegeneration5
- It suggests that mitochondrial recycling is critical to maintaining healthy mitochondria, and disruptions to this process can contribute to neurodegeneration … Our future studies will investigate how these pathways contribute to disease and how they can be targeted therapeutically. (genengnews.com)
- This study suggests the enhancement of Δp by mito-dR as a therapeutic mechanism that ameliorates neurodegeneration by protecting mitochondrial functions. (nature.com)
- Here, we investigated whether this aberrant Cdk5 signalling contributes to the striatal neurodegeneration by altering mitochondrial dynamics processes. (bmj.com)
- 4Paoletti P, Vila I, Rifé M, Lizcano JM, Alberch J, Ginés S. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin dependent kinase 5. (bmj.com)
- However, he said that "while very interesting findings, this is really the first effort that demonstrates how damaged mitochondrial DNA may contribute to neurodegeneration in the context of PD and PD dementia. (medscape.com)
MELAS2
- MELAS is a complicated, multisystem disease. (medscape.com)
- Mitochondrial dysfunction characterized in human induced pluripotent stem cell disease models in MELAS syndrome: A brief summary. (bvsalud.org)
Genetically2
- Dr. Ganesh says mitochondrial diseases are genetically inherited. (mdlinx.com)
- Objectives To develop a cohort of 1000 people from across the UK with biochemically, and/or genetically, confirmed mitochondrial disease to facilitate large-scale interventional trials of drugs and novel treatments, and to assess prevention strategies. (bmj.com)
Pathology4
- Previous analyses of dopaminergic (DAergic) neurons from patients with Lewy-body pathology revealed a deficiency in nuclear-encoded genes for mitochondrial respiration, many of which are targets for the transcription factor estrogen-related receptor gamma ( Esrrg /ERRγ). (nature.com)
- Laser-captured microdissected (LCM) DAergic neurons from postmortem tissue of patients with Lewy-pathology revealed a deficiency in expression for nuclear-encoded genes involved in mitochondrial respiration and function 12 . (nature.com)
- Collectively, these results suggest that abnormal accumulation of APP across mitochondrial import channels, causing mitochondrial dysfunction, is a hallmark of human AD pathology. (jneurosci.org)
- VHIR Neuromuscular and Mitochondrial Pathology research group is looking for a Researcher with Bachelor/Master degree and sufficient experience in biomedical research in the area of mitochondrial function. (ibecbarcelona.eu)
Function10
- Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. (wikipedia.org)
- Most mitochondrial function and biogenesis is controlled by nuclear DNA. (wikipedia.org)
- Mitochondrial disease or dysfunction, as it's also called, happens when something causes a change in the mitochondria, so they can't produce enough energy for a cell or organ to function properly. (chop.edu)
- Given the complexity of the biological function of mitochondria, researchers have begun to consider rescuing the injured cells through mitochondrial transfer, that is, replacing damaged mitochondria with healthy mitochondria from donor cells. (frontiersin.org)
- While ERRγ deletion did not fully recapitulate the transcriptional alterations observed in postmortem tissue, it caused reductions in genes involved in synaptic and mitochondrial function and autophagy. (nature.com)
- Further evidence suggests that during PD progression, transcriptional programs for the expression of genes involved in mitochondrial structure and function are disrupted 11 . (nature.com)
- This vicious cycle continually worsens mitochondrial and immune system function, which promotes the occurrence of chronic conditions and severe disease. (holtorfmed.com)
- The disruption of mitochondrial function is known to be linked to neurodegenerative diseases. (bmglabtech.com)
- The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. (benthamscience.com)
- Is this still the general recommendation to maximize energy and mitochondrial function? (umdf.org)
Genes mutated1
- One, using cell reprogramming, was aimed at patients who have only some-say, 30% to 40%-of their mitochondrial genes mutated. (foxnews.com)
Mito8
- Welcome to Mito 101, your introduction to mitochondria, mitochondrial disease, how it's treated today and what's ahead. (chop.edu)
- Is Mitochondrial Disease (Mito) Causing Your Health Issues? (holtorfmed.com)
- Is Mitochondrial Disease (Mito) the Cause of Your Health Issues? (holtorfmed.com)
- Mitochondrial disease is often referred to as "mito. (holtorfmed.com)
- MitoAction Programs create positive impacts in the lives of people with mito disease and their families. (mitoaction.org)
- Light-dependent activation of mitochondrion-targeted dR (mito-dR) but not a mito-dR inactive mutant successfully transformed mitochondria from an OXPHOS-dependent powerhouse to a photoenergetic powerhouse, which accordingly reinforced the mitochondrial functions of the nerve terminals in terms of ATP production and Ca 2+ -buffering activity, suppressing ROS generation 10 , 11 . (nature.com)
- Noah, who normally gets around in a wheelchair he calls Bumblebee, was born with Mitochondrial disease (known as mito) - a debilitating and potentially fatal condition that reduces the ability of mitochondria to produce energy. (vsk.org.au)
- If you missed the December 2020 'Ask the Mito Doc' webcast, 'Diet and Nutrition - Managing Mitochondrial Disease through the Holidays' watch the replay below. (umdf.org)
Neuromuscular1
- This is very well exemplified in the shift from descriptive classifications of neuromuscular diseases to molecular pathobiologic classifications of neuromuscular diseases. (medscape.com)
Seizures2
- In mitochondrial diseases, medically resistant or highly resistant prolonged seizures were more common than in the other groups of patients studied, and mortality was also high in these patients. (oulu.fi)
- Seizures are a common and highly heterogeneous feature of mitochondrial disease. (medscape.com)
Neurodegenerative disease2
- Loss of basal macroautophagy in animals leads to pronounced neurodegenerative disease. (helsinki.fi)
- 1 Excessive production of reactive oxygen species can lead to oxidative stress which is associated with inflammation and neurodegenerative disease. (bmglabtech.com)
Interestingly1
- Interestingly, mitochondrial translocation of APP was incomplete because of an internal acidic domain present between 220 and 290 amino acids. (jneurosci.org)
Processes2
- If a chemical compound targeting one of these hubs is used, it can not only modify the anticipated biological pathways but also change other unexpected mitochondrial processes ( 5 ). (frontiersin.org)
- We have shown that epigenetic changes occur in AD brain implicating these processes in disease. (neurodegenerationresearch.eu)
Occur1
- Mitochondrial dysfunction may also occur in a host of other medical conditions as well as from medications or environmental exposures. (chop.edu)
Adults2
- These diseases are often fatal, and typically affect children, although adults are diagnosed as well. (mdlinx.com)
- The British Neurology Surveillance Unit and British Paediatric Neurology Surveillance Unit have been utilised to identify patients not under active follow-up at one of the three centres (Newcastle, London and Oxford) providing the NHS Highly Specialised Service for Rare Mitochondrial Diseases in Adults and Children. (bmj.com)
Chronic1
- However, it takes a high percentage of heavily damaged mitochondria to induce chronic disease. (holtorfmed.com)