{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytochrome c oxidase subunit I (COX1) is a core catalytic component of the mitochondrial electron transport chain that drives oxidative phosphorylation and ATP generation. Its synthesis is tightly regulated by dedicated mitochondrial translational activators such as TACO1, whose deficiency leads to impaired COX1 production and cytochrome c oxidase deficiency underlying disorders like late‐onset Leigh syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, cellular quality‐control mechanisms, exemplified by Parkin‐mediated clearance of defective mitochondria harboring deleterious COX1 mutations, serve to restore cytochrome c oxidase activity and maintain optimal respiratory function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, investigations into the epigenetic regulation of mitochondrial genes have demonstrated that the methylation status of the COX1 (MT‐CO1) gene remains unassociated with disease severity in conditions such as nonalcoholic fatty liver disease, highlighting its essential and stable role in mitochondrial bioenergetics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings emphasize that COX1 is vital for electron transport and energy metabolism, and its proper synthesis and maintenance are critical for cellular health; disruptions in COX1 expression or function can precipitate mitochondrial dysfunction and contribute to disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Woranontee Weraarpachai, Hana Antonicka, Florin Sasarman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.390"}], "href": "https://doi.org/10.1038/ng.390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19503089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19503089"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Der-Fen Suen, Derek P Narendra, Atsushi Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0914569107"}], "href": "https://doi.org/10.1073/pnas.0914569107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20547844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20547844"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carlos Jose Pirola, Tomas Fernández Gianotti, Adriana Laura Burgueño, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2012-302962"}], "href": "https://doi.org/10.1136/gutjnl-2012-302962"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22879518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22879518"}]}]}]}