{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP8 is one of the two mitochondrially encoded subunits produced from a bicistronic mRNA together with ATP6 and forms an essential component of the F‐ATP synthase (complex V) responsible for ATP production via oxidative phosphorylation. ATP8 contributes to the proper assembly and structural stabilization of ATP synthase, ensuring efficient coupling of proton flow to ATP synthesis. Perturbations in the expression or processing of the ATP8/ATP6 bicistronic transcript adversely affect complex V assembly and function, leading to impaired ATP production, increased formation of reactive oxygen species, and altered mitochondrial membrane potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Clinical investigations have linked mutations in the MT-ATP6/MT-ATP8 region to a spectrum of mitochondrial disorders – including Charcot–Marie–Tooth disease, Leigh syndrome, and episodes of limb weakness – which have been attributed to defective ATP synthase assembly and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, recent studies have identified specific polymorphisms in ATP8 that alter mitochondrial performance by increasing oxidative stress, thereby heightening susceptibility to autoimmune disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, ATP8 has been shown to serve as a critical binding partner for nuclear-encoded factors such as PRICKLE3, which interact with ATP8 to support the assembly and stability of the ATP synthase complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these findings underscore that ATP8 is vital not only for bioenergetic function but also for maintaining mitochondrial integrity, with its dysregulation contributing to diverse pathological phenotypes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard J Temperley, Sara H Seneca, Katarzyna Tonska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddg238"}], "href": "https://doi.org/10.1093/hmg/ddg238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12915481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12915481"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Karine Auré, Odile Dubourg, Claude Jardel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000436067.43384.0b"}], "href": "https://doi.org/10.1212/01.wnl.0000436067.43384.0b"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24153443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24153443"}]}, {"type": "r", "ref": 3, "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": 4, "children": [{"type": "t", "text": "A-R Moslemi, N Darin, M Tulinius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two new mutations in the MTATP6 gene associated with Leigh syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-2005-872845"}], "href": "https://doi.org/10.1055/s-2005-872845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16217706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16217706"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xinhua Yu, Lena Wester-Rosenlöf, Ulrike Gimsa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mtDNA nt7778 G/T polymorphism affects autoimmune diseases and reproductive performance in the mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp432"}], "href": "https://doi.org/10.1093/hmg/ddp432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19759059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19759059"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jialing Yu, Xiaoyang Liang, Yanchun Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI134965"}], "href": "https://doi.org/10.1172/JCI134965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32516135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32516135"}]}]}]}