{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The mitochondrial gene ATP6 encodes a core subunit of the F₁F₀-ATP synthase (complex V), playing a vital role in coupling proton transport to ATP production. Variation in ATP6 can modify mitochondrial efficiency and underlie diverse clinical phenotypes. For instance, a specific ATP6 single‐nucleotide polymorphism (SNP 9055A) was associated with a decreased risk of Parkinson disease—an effect more pronounced in women."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, mutations at nucleotide 8993 (T>G and T>C) disrupt ATP synthesis by impairing the assembly and stability of complex V; such defects lead to energy deprivation and increased reactive oxygen species production that contribute to neuropathy, ataxia, retinitis pigmentosa, and the spectrum of neurological dysfunction observed in NARP (Neuropathy, Ataxia and Retinitis Pigmentosa) patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, the m.9185T>C mutation in ATP6 has been shown to impair complex V assembly and activity, thereby leading to axonal neuropathies such as Charcot‐Marie‐Tooth disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, high levels of ATP6 mutations correlate with defective ATP synthase function and diminished ATP production, which have been implicated in severe early‐onset disorders, including Leigh syndrome, through impaired complex V stability and efficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n These findings collectively emphasize that ATP6 is essential for optimal oxidative phosphorylation and that its disruption can lead to a wide variety of mitochondrial dysfunctions and neurodegenerative diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joelle M van der Walt, Kristin K Nicodemus, Eden R Martin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/373937"}], "href": "https://doi.org/10.1086/373937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12618962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12618962"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Giovanni Manfredi, Jin Fu, Joseline Ojaimi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2007.05.005"}], "href": "https://doi.org/10.1016/j.bbabio.2007.05.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17568559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17568559"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Robert D S Pitceathly, Sinéad M Murphy, Ellen Cottenie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0b013e3182698d8d"}], "href": "https://doi.org/10.1212/WNL.0b013e3182698d8d"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22933740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22933740"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eva Morava, Richard J Rodenburg, Frans Hol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and biochemical characteristics in patients with a high mutant load of the mitochondrial T8993G/C mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.31194"}], "href": "https://doi.org/10.1002/ajmg.a.31194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16532470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16532470"}]}]}]}