Ecto-F1F0 ATP synthase/F-1 ATPase: metabolic and immunological functions

Purpose of review Until recently, F1F0 ATP synthase expression was believed to be strictly confined to mitochondria where it generates most cellular ATP. This paper reviews the recent evidence for an extra-mitochondrial expression of its components by immunofluorescence, biochemistry and proteomics studies. It discusses its possible implications in an ecto-nucleotide metabolism and its pathophysiological role in normal and tumoral cells. Recent findings F1F0 ATP synthase components have been identified as cell-surface receptors for apparently unrelated ligands in the course of studies carried out on angiogenesis, lipoprotein metabolism, innate immunity, hypertension, or regulation of food intake. Summary F1F0 ATP synthase is expressed on endothelial cells where it binds angiostatin, regulates surface ATP levels, and modulates endothelial cell proliferation and differentiation. Through binding of apolipoprotein A-I, a similar complex, expressed on hepatocytes, regulates lipoprotein internalization. On tumors, it is-recognized in association with apolipoprotein A-I by the antigen receptor of circulating cytotoxic lymphocytes of the gamma delta subtype and thus promotes an innate tumor cell recognition and lysis. It binds enterostatin on brain cells. Biochemistry and proteomics studies indicate an enrichment of F, F. components in lipid rafts selectively with some other mitochondrial proteins, suggesting intracellular traffic connection's between mitochondria and other membrane compartments. Finally, depending on cell type and environment, it can generate ATP or ADP which may transfer a downstream signal to purinergic receptors.