Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mRNA levels of ATPase beta, ATPase 6, cytochrome oxidase (COX) VIb and COX I subunits were found to be 2.4-13.8-fold higher in brown adipose tissue (BAT) than in heart, skeletal muscle, brain and liver of mice. The comparison with tissue contents of ATPase and COX revealed that the selective, 5-11-fold reduction of ATPase in BAT is not caused by decreased transcription of ATPase genes. Likewise, the ATPase beta and COX VIb mRNA levels in cultured brown adipocytes were also not influenced by norepinephrine, which activated the expression of the UCP gene by two orders of magnitude. The results indicate that the biosynthesis of mitochondrial ATPase in BAT is post-transcriptionally regulated.
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PMID:Low content of mitochondrial ATPase in brown adipose tissue is the result of post-transcriptional regulation. 166 83

Sequence analysis of the mitochondrial ATPase 6 gene from chicken revealed that its 3' region is virtually identical with a chicken muscle-specific 7 S RNA which was reported to induce the expression of tissue-specific functions in blastoderm explants. Using chicken and quail cell lines depleted of mitochondrial DNA, we demonstrate that the 7 S RNA is encoded by the mitochondrial genome and not by nuclear (repetitive) DNA as suggested previously. Moreover, no 7 S RNA-homologous transcript of the expected length (about 400 bases) is detected, either in these cell lines or in heart and liver tissues. The only RNA species hybridizing with a 7 S RNA-specific probe is an abundant, 900 base long transcript of mitochondrial origin that we identify as the ATPase 8-ATPase 6 fused messenger. We suggest that the characterized muscle-specific 7 S RNA cDNA is derived from an unrelated contaminant in the blastoderm-inducing fraction.
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PMID:Putative chicken "muscle-specific 7 S RNA" is related to the mitochondrial ATPase 6 gene. 247 59

We have cloned and sequenced human and bovine cDNAs for the beta subunit of the ATP synthase (ATP-syn beta), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsyn beta was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsyn beta proved to be 1.9 x 10(-9) substitutions per site per year (substitutions x site-1 x year-1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the "selective constraint ratio". This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS.
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PMID:Sequence analysis of cDNAs for the human and bovine ATP synthase beta subunit: mitochondrial DNA genes sustain seventeen times more mutations. 289 50

Using an antiserum generated against a synthetic peptide predicted from the DNA sequence of the ATPase 6 gene of the mitochondrial DNA, we demonstrate that mitochondria from two oligomycin-resistant Chinese hamster ovary cell lines with a defined mutation in the ATPase 6 gene synthesize an altered ATPase 6 gene product. This altered gene product migrates in sodium dodecyl sulfate-polyacrylamide gels as if it has a molecular mass that is larger by 1000 daltons than the wild-type ATPase 6 gene product. We also demonstrate that mitochondria from four other independently isolated oligomycin-resistant Chinese hamster ovary mutant cell lines contain a similar altered ATPase 6 gene product. These results suggest that all six oligomycin-resistant cell lines have a similar mutation in the ATPase 6 gene of the mitochondrial DNA that encodes subunit 6 of the ATP synthase complex.
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PMID:Altered form of subunit 6 of mitochondrial ATP synthase complex in oligomycin-resistant mutants of Chinese hamster ovary cells. 297 Jun 80

We have determined the nucleotide sequence of the URF A6L and ATPase 6 genes of the mitochondrial DNA of wild-type Chinese hamster ovary (CHO) cells and of two independently isolated, cytoplasmically inherited CHO mutant cell lines that are resistant to oligomycin, an inhibitor of the mitochondrial ATP synthase (ATPase) complex. Comparison of the nucleotide sequences of the mutants with that of their parental cell line revealed a single nucleotide difference, a G-to-A transition at nucleotide 433 of the ATPase 6 gene. This single base pair change predicts a nonconservative amino acid change, with a glutamic acid residue being replaced by a lysine residue at amino acid 145 of the ATPase 6 gene product in the mutants. This glutamic acid residue and several others in the surrounding amino acid sequence are conserved among all species examined to date. Analyses of several of the biochemical properties of the oligomycin-resistant CHO mutants indicate that the glutamic acid residue at position 145 of subunit 6 of the mitochondrial ATP synthase complex is important for the binding of oligomycin to the enzyme complex, but is not essential for proton translocation.
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PMID:Mitochondrial DNA of two independent oligomycin-resistant Chinese hamster ovary cell lines contains a single nucleotide change in the ATPase 6 gene. 301 40

A family is described with a T-->G mutation at position 8993 of mtDNA. This mutation is located in the ATPase 6 gene of mtDNA which encodes subunit a of the ATP-synthase complex (FlFo-ATPase). Clinically, the patients showed severe infantile lactate acidosis and encephalomyopathy in a form that was different from the classical Leigh syndrome. In 3 affected boys, ranging in age from 3 months to 8 years, the mutation was found in 95-99% of the mtDNA population. The clinical symptoms correlated with the mtDNA heteroplasmy and in the healthy mother 50% of the mtDNA was mutated. The rate of mitochondrial ATP production by cultured skin fibroblasts containing 99% of mutated mtDNA was about 2-fold lower than that in normal fibroblasts. Native electrophoresis of the mitochondrial enzyme complexes revealed instability of the FlFo-ATPase in all the tissues of the patient that were investigated (heart, muscle, kidney, liver). Only a small portion of the ATP-synthase complex was present in the complete, intact form (620 kDa). Incomplete forms of the enzyme were present as subcomplexes with approx. molecular weights of 460, 390 and 150 kDa, respectively, which differed in the content of F1 and Fo subunits. Immunochemical analysis of the subunits of the FlFo-ATPase further revealed a markedly decreased content of the Fo subunit b in mitochondria from muscle and heart, and an increased content of the Fo subunit c in muscle mitochondria, respectively. These results indicate that in this family the T-->G point mutation at position 8993 in the mitochondrial ATPase 6 gene is accompanied by structural instability and altered assembly of the enzyme complex, that are both most likely due to changes in the properties of subunit a of the membrane sector part of the ATP-synthase.
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PMID:Altered properties of mitochondrial ATP-synthase in patients with a T-->G mutation in the ATPase 6 (subunit a) gene at position 8993 of mtDNA. 760 2

A T-to-C transition at nucleotide (nt) 9176 in the mitochondrial adenosine triphosphatase 6 (ATPase 6) gene was detected in 2 brothers with a neurological disorder resembling Leigh syndrome. The mutation was also present in the 2 other siblings and in the mother, who were asymptomatic. In the more severely affected boy (the proband), the mutation was homoplasmic in muscle, leucocytes, and fibroblasts. In leucocytes from his affected brother, 98% of mtDNA was mutant. Heteroplasmy of varying degrees was seen in leucocytes from the mother and the 2 unaffected siblings. The mutation changes a highly conserved leucine residue near the carboxyl terminus of the mitochondrial ATPase 6 subunit to proline. It could not be detected in 168 control subjects. Studies of ATP synthesis and hydrolysis in fibroblasts from the proband were normal.
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PMID:A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis. 766 37

The relative concentrations of several subunits of the mitochondrial F0.F1-ATP synthase were determined in mitochondria and submitochondrial particles prepared from the livers of ethanol-fed and control rats. The polypeptides were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis and the stained gels were analyzed by densitometry for the relative concentrations of the ATP synthase subunits. A significant decrease in the relative concentration of the mitochondrial gene product, ATPase subunit 8, was observed in mitochondria and submitochondrial particles from ethanol-fed animals. The relative concentration of the other mitochondrial encoded ATPase subunit, ATPase 6, was also depressed, as confirmed in submitochondrial particles. In contrast, there were no significant ethanol-related depressions in subunits alpha, beta, and OSCP of the F0.F1 or the adenine nucleotide carrier in intact mitochondria. These results demonstrate that ethanol consumption causes a decrease in the content of mitochondrial synthesized subunits 6 and 8 whereas no effect is exerted on the concentrations of nuclear gene products of the ATP synthase complex. Likewise, the adenine nucleotide transporter, also a nuclear gene product, is unaffected by ethanol consumption.
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PMID:Differential effects of ethanol consumption on synthesis of cytoplasmic and mitochondrial encoded subunits of the ATP synthase. 797 8

A 5-year-old child with clinical and radiologic evidence of Leigh syndrome (LS) showed a T-->C mutation at position nt 8993 in the mitochondrial DNA (instead of the more common T-->G substitution), resulting in an amino acid change from a highly conserved leucine to proline in subunit 6 of mitochondrial ATPase. The mutation was heteroplasmic and maternally inherited, and was present in high percentages in multiple tissues. This finding documents genetic heterogeneity of the ATPase 6 gene mutation associated with LS.
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PMID:A T-->C mutation at nt 8993 of mitochondrial DNA in a child with Leigh syndrome. 819 Mar 10

The mitochondrial ATPase 6 gene encodes a subunit of F1F0 adenosine triphosphate (ATP) synthase. A mutation in the ATPase 6 gene has been genetically linked to two maternally inherited genetic diseases: neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) and certain cases of subacute necrotizing encephalopathy (SNE). Although the severity of both NARP and SNE disease were correlated with the quantity of the ATPase 6leu156-->arg mutation in each patient, the mutation could not be shown to alter F1F0-ATP synthase activity. To investigate the biochemical effects of the ATPase 6leu156-->arg mutation on F1F0-ATP synthase, the aleu207-->arg mutation was constructed in the F1F0-ATP synthase from Escherichia coli to serve as a model for the disease mutation. Characterization of the model bacterial enzyme revealed that the mutation abolishes detectable ATP synthesis via oxidative phosphorylation. The aleu207-->arg mutation results in a structural perturbation blocking proton translocation through F1F0-ATP synthase. The results suggest that a structural defect in human F1F0-ATP synthase is the biochemical basis for NARP and SNE.
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PMID:The aleu207-->arg mutation in F1F0-ATP synthase from Escherichia coli. A model for human mitochondrial disease. 850 61


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