{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP5MK, also known as DAPIT and encoded by the USMG5 gene, is a small, highly conserved subunit of the mitochondrial F‐ATP synthase complex that is critical for the assembly, stability, and dimerization of the enzyme. Its proper incorporation into ATP synthase is essential for maintaining adequate ATP production, and alterations in ATP5MK levels can markedly influence mitochondrial respiration and cellular energy metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cell models, suppression or knockdown of ATP5MK results in the loss of the ATP synthase population within mitochondria, decreased ATP synthesis, and associated impairments in cell growth and survival, particularly under conditions of metabolic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Conversely, over‐expression of ATP5MK has been reported to disturb mitochondrial homeostasis by reducing mitochondrial mass and altering proton gradient balance, which contributes to a shift toward anaerobic metabolism and even promotes phenotypic changes such as epithelial-to-mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In pathological contexts, ATP5MK plays an adaptive or protective role; for instance, in diabetic nephropathy and heart failure models, its regulated expression is associated with a reduction in fibrosis and improved cardiac function, highlighting its importance in energy maintenance under stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, genetic disruption of ATP5MK has been linked to severe clinical syndromes such as Leigh syndrome, where compromised ATP synthase dimerization leads to impaired ATP production and devastating neurological outcomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and alterations in its expression may also contribute to neuropsychiatric conditions like schizophrenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, emerging evidence in muscular dystrophy models indicates that ATP5MK is part of a regulatory cascade modulated by microRNAs and translational factors that ultimately governs mitochondrial ATP synthesis, suggesting that modulation of ATP5MK may be therapeutically relevant in conditions of muscle degeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shigenori Ohsakaya, Makoto Fujikawa, Toru Hisabori, et al. 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