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since 01/2001:

OKDB#: 938
 Symbols: ATP6 Species: human
 Synonyms: ATPase6, MTATP6  Locus:

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General Comment Complex V (ATP synthase) of the mitochondrion comprises 10-16 subunits encoded by nuclear DNA and 2 subunits (ATPase 6 and ATPase 8) encoded by mtDNA. Subunit 6 of mitochondrial ATP synthase (complex V) is encoded by nucleotides 8527-9207 of the mitochondrial genome. ////////Leigh syndrome; A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Holt IJ et al. (1990) A variable combination of developmental delay, retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy occurred in four members of a family and was maternally transmitted. There was no histochemical evidence of mitochondrial myopathy. Blood and muscle from the patients contained two populations of mitochondrial DNA, one of which had a previously unreported restriction site for AvaI. Sequence analysis showed that this was due to a point mutation at nucleotide 8993, resulting in an amino acid change from a highly conserved leucine to arginine in subunit 6 of mitochondrial H(+)-ATPase. There was some correlation between clinical severity and the amount of mutant mitochondrial DNA in the patients; this was present in only small quantities in the blood of healthy elderly relatives in the same maternal line.//////////////////
General function DNA Replication, Enzyme
Cellular localization Mitochondrial
Ovarian function Oogenesis, Early embryo development
Comment Lee et al 2000 studied mitochondrial ATPase 6 gene expression in unfertilized oocytes and cleavage-stage embryos Reverse transcription polymerase chain reaction was performed in unfertilized oocytes and cleavage-stage embryos derived from tripronucleate embryos to determine ATPase 6 gene expression. Comparison of ATPase 6 gene expression by using single-cell reverse transcription polymerase chain reaction. Expression of unfertilized oocytes is lower compared with early cleavage-stage embryos.
Expression regulated by
Ovarian localization Oocyte
Follicle stages Preovulatory
Phenotypes POF (premature ovarian failure)
Mutations 2 mutations

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Oxidative stress and ATPase6 mutation is associated with primary ovarian insufficiency. Venkatesh S et al. PURPOSE: Primary ovarian insufficiency (POI) is a heterogeneous, multifactorial disorder. Though genetic anomalies, infections, autoimmune disorder and hormonal imbalance are few of the causes of POI, in the majority of patients (50-60%) no etiology has been identified. Mitochondrial bioenergetics and biogenesis play an important role in oocyte and embryo development, whereas mtDNA integrity and content are essential for the normal development of oocytes. ATPase6 helps to maintain the mt genome integrity, and mutations in ATPase6 are associated with overproduction of reactive oxygen species (ROS) in a variety of diseases; however, its role in POI has not been evaluated. Therefore, we planned to evaluate the potential role of ATPase6 gene mutations and associated oxidative stress in idiopathic cases of POI. METHODS: This pilot study included: 20 cases of POI with FSH level of >40 mIU/ml; 4 cases of occult ovarian insufficiency (occult OI) with irregular menses and mean FSH levels of 16.4 mIU/ml; and 20 age-matched healthy female controls (FSH 2-5 mIU/ml). ROS levels in blood plasma were measured by luminol-dependent chemiluminescence assay and the ROS values were expressed as relative light unit per minute (RLU/min). mtDNA ATPase6 gene was amplified and sequenced from the blood lymphocyte DNA. RESULTS: Of all, 50% patients showed nucleotide changes in the ATPase6 gene, as compared to 10% in controls, and the majority of these mutations were non-synonymous. ATPase6 mt.8684 C>T and mt.9094 C>T were found to be significantly (P < 0.005) higher in cases as compared to controls. ROS levels were found to be significantly (P < 0.005) higher in POI and occult OI patients compared to controls and nucleotide changes were found to positively correlate with ROS levels. Moreover, ROS production was found to positively correlate (r = 0.7038, P < 0.001) with FSH levels of the patients (POI and OI) compared to controls. CONCLUSIONS: This pilot study clearly demonstrates for the first time ATPase6 gene nucleotide alterations and elevated ROS levels in idiopathic cases of POI. Therefore, it may be possible that OS associated with ATPase6 gene mutation may be causal in idiopathic cases of premature OI. However, larger studies with inclusion of more cases of both POI and occult OI are required to strongly establish the correlation between oxidative stress and mitochondrial nucleotide alterations in the pathogenesis of POI. Such cases with OS-induced POI may benefit immensely by early diagnosis and prompt antioxidant administration.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Expression of the mitochondrial ATPase6 gene and Tfam in Down syndrome. Lee SH et al. We investigated the expression of the mitochondrial ATPase6 gene whose product is active in oxidative phosphorylation (OXPHOS), and compared it to the expression of Tfam, an important regulator of the transcription and replication of mtDNA. Our aim was to examine a possible relation between mitochondrial gene expression and Down syndrome. The expression of ATPase6 and Tfam was analyzed by RT-PCR amplification of the mRNA in cultured amniocytes from Down syndrome and normal fetuses. The band intensities obtained were normalized against those of HPRT. The Down syndrome fetuses were found to have lower ATPase6 and Tfam expression than the normal fetuses. This finding suggests that mitochondrial dysfunction resulting from decreased ATPase6 and Tfam expression during meiotic oocyte maturation of oocytes might affect ATP generation and cause the nondisjunctional error. Hence this study suggests that mitochondrial dysfunction may be associated with the developmental mechanism of Down syndrome.

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created: May 30, 2000, midnight by: hsueh   email:
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last update: Oct. 6, 2016, 2:17 p.m. by: hsueh    email:

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