Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A maternally inherited and practically homoplasmic mitochondrial (mtDNA) mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No alternate Met codon could replace the normal translational initiator. The patient harboring this mutation exhibited clinical symptoms suggesting a mitochondrial disease but his mother who carried the same mtDNA mutation was healthy. The mutation was absent from 100 controls and occurred once amongst 44 patients suspected of Leber Hereditary Optic Neuropathy (LHON) but devoid of typical LHON mutations. In patient fibroblasts, no effect of 8527A>G mutation could be demonstrated on the biosynthesis of mtDNA-encoded proteins, on size and the content of ATPase subunit a, on ATP hydrolysis and on mitochondrial membrane potential. In addition, ATP synthesis was barely decreased. Therefore, GUG is a functional initiation codon for the human ATP6 gene.
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PMID:GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene. 1469 45

F1Fo-ATP synthase is a key enzyme of mitochondrial energy provision producing most of cellular ATP. So far, mitochondrial diseases caused by isolated disorders of the ATP synthase have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors TMEM70 and ATPAF2. Here, we describe a patient with a homozygous p.Tyr12Cys mutation in the epsilon subunit encoded by the nuclear gene ATP5E. The 22-year-old woman presented with neonatal onset, lactic acidosis, 3-methylglutaconic aciduria, mild mental retardation and developed peripheral neuropathy. Patient fibroblasts showed 60-70% decrease in both oligomycin-sensitive ATPase activity and mitochondrial ATP synthesis. The mitochondrial content of the ATP synthase complex was equally reduced, but its size was normal and it contained the mutated epsilon subunit. A similar reduction was found in all investigated F1 and Fo subunits with the exception of Fo subunit c, which was found to accumulate in a detergent-insoluble form. This is the first case of a mitochondrial disease due to a mutation in a nuclear encoded structural subunit of the ATP synthase. Our results indicate an essential role of the epsilon subunit in the biosynthesis and assembly of the F1 part of the ATP synthase. Furthermore, the epsilon subunit seems to be involved in the incorporation of subunit c to the rotor structure of the mammalian enzyme.
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PMID:Mitochondrial ATP synthase deficiency due to a mutation in the ATP5E gene for the F1 epsilon subunit. 2056 10

Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype.
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PMID:Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene. 2503 80

Background. The mutation 9185T>C in ATP6 gene, associated with Leigh syndrome, was reported in only few families. Motor neuron disease (MND), both clinically and electrophysiologically, was not previously described in association with this mutation. Case Report. 33-year-old male, with family history of mitochondrial disease, presented with cognitive impairment, exercise intolerance, and progressive muscle weakness. Examination revealed global hypotonia, and proximal tetraparesis, without atrophy or fasciculation, pyramidal signs, or sensory symptoms. The laboratory findings revealed an increase of lactate and lactate/pyruvate ratio; electromyogram showed chronic neurogenic compromise; muscle biopsy was suggestive of spinal muscular atrophy and mitochondriopathy; genetic study of SMN1 was negative but detected a homoplasmic mutation 9185T>C in ATP6 gene. His younger sister, with the same mutation, had cognitive impairment, ataxia, and muscle weakness. EMG showed axonal peripheral neuropathy. Conclusion. This case is unique because of the benignity and the coexistence of clinical, neurophysiological, and pathological findings suggestive of MND that, although described in mitochondrial disease, have not yet been reported in association with 9185T>C mutation. The present case contributes to the expansion of the phenotypic expressions of this particular mutation.
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PMID:Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6. 2554 92

The mitochondrial disease often associated with various illnesses in relation to the activity of cells metabolites and the synthesis of adenosine triphosphate (ATP), including alteration in the mitochondrial DNA. The mutation of m.9053G>A at the ATP6 gene was found in patients with type 2 diabetes mellitus (DM type 2) and cataract. Therefore, this mutation is predicted to be clinical features of the 2 diseases. ATP6 gene encodes protein subunit of ATPase6, a part of ATP synthase, which is important in the electron transfer and proton translocation in intracellular respiration system. This study aims to investigate the mutation effect of m.9053G>A at the ATP6 gene (S167N) to the structure and function of ATPase6 using bioinformatics method. The structure of ATPase6 was constructed using homology modeling method. The crystal structure of bovine's ATP synthase (Protein Data Bank ID 5FIL) was used as a template because of high sequence similarity (77%) and coverage (96%) of the input sequence. The effect of mutation was investigated at the proton translocation channel of ATPase6. It is predicted that the channel was disrupted due to changes in electrostatic potential from serine to asparagine. Furthermore, molecular docking suggests that water binding on the proton translocation channel in the S167N mutant was different from the wild type. The result of this study is hoped to be useful in the development of a new genetic marker for DM type 2 and cataract.
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PMID:Bioinformatics Study of m.9053G>A Mutation at the ATP6 Gene in Relation to Type 2 Diabetes Mellitus and Cataract Diseases. 2893 7

The glacier ice worm, Mesenchytraeus solifugus, is among a few animals that reside permanently in glacier ice. Their adaptation to cold temperature has been linked to relatively high intracellular adenosine triphosphate (ATP) levels, which compensate for reductions in molecular motion at low physiological temperatures. Here, we show that ATP6-the critical regulatory subunit of the F1Fo-ATP synthase and primary target of mitochondrial disease-acquired an unprecedented histidine-rich, 18-amino acid carboxy-terminal extension, which counters the strong evolutionary trend of mitochondrial genome compaction. Furthermore, sequence analysis suggests that this insertion is not of metazoan origin, but rather is a product of horizontal gene transfer from a microbial dietary source, and may act as a proton shuttle to accelerate the rate of ATP synthesis.
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PMID:Atypical Evolution of the F1Fo Adenosine Triphosphate Synthase Regulatory ATP6 subunit in Glacier Ice Worms (Annelida: Clitellata: Mesenchytraeus). 3002 8