{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATP5PF – which encodes a component of the mitochondrial ATP synthase complex often known as coupling factor 6 (CF6) – plays dual roles in cellular energy metabolism and in intercellular signaling. As a core element of the ATP synthase machinery, ATP5PF contributes to oxidative phosphorylation within the mitochondria, thereby facilitating ATP production. In addition, a portion of ATP5PF/CF6 is displayed on the plasma membrane of endothelial and vascular smooth muscle cells, where it acts as an extracellular ligand. Binding of CF6 to the β‐subunit of cell surface ATP synthase promotes ATP hydrolysis, leading to intracellular acidification, inhibition of phospholipase A₂ activity, and suppression of prostacyclin and nitric oxide production. Such actions contribute to enhanced Ca²⁺ signaling and vasoconstriction, which have been implicated in the development of hypertension and cardiac dysfunction in several disease contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel with its role in regulating vascular tone and blood pressure, dysregulation of ATP synthase subunits related to ATP5PF has been observed in pathological states including metabolic disease and cancer. Altered expression of CF6 or related subunits can modulate signaling pathways that influence cell migration, chemotherapeutic sensitivity, and overall cellular energy balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, animal models have shown that increased circulating CF6 is associated with insulin resistance, enhanced renin–angiotensin system activity, and salt‐sensitive hypertension, highlighting its broader impact on cardiovascular and metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ATP5PF functions not only as an essential subunit of the mitochondrial ATP synthase necessary for efficient energy production, but also as an extracellular modulator of vascular and metabolic signaling. This dual functionality positions ATP5PF/CF6 as a potential contributor to cardiovascular dysfunction and as a therapeutic target in conditions such as hypertension, myocardial infarction, and certain cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomohiro Osanai, Koji Magota, Makoto Tanaka, et al. 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