Cell surface F1Fo ATP synthase: a new paradigm?
The mitochondrial F1Fo adenosine triphosphate (ATP) synthase is one of the most thoroughly studied enzyme complexes known. Yet, a number of new observations suggesting that the enzyme is also located on the cell surface necessitate further investigation. While the mitochondrial synthase utilizes the proton gradient generated by oxidative phosphorylation to power ATP synthesis, the cell surface synthase has instead been implicated in numerous activities, including the mediation of intracellular pH, cellular response to antiangiogenic agents, and cholesterol homeostasis. Intriguingly, a common thread uniting these various models of cell surface ATP synthase functions is the apparently caveolar distribution of the enzyme. Recent studies concerning the cell surface ATP synthase manifest applications in the regulation of serum cholesterol levels, cellular proliferation and antitumor strategies. This review addresses the expression, interactions, functions, and consequences of inhibition of cell surface ATP synthase, an enzyme now displaying a shift in paradigm, as well as of location.
Chi
Sulene L
SL
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Pizzo
Salvatore V
SV
D043168:Angiostatins / Q000502:physiology; D021941:Caveolae / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D003602:Cytotoxicity, Immunologic; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008075:Lipoproteins, HDL / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D008075:Lipoproteins, HDL; C440036:P2RY13 protein, human; D018110:Receptors, Lipoprotein; D018048:Receptors, Purinergic P2; D043168:Angiostatins; D006180:Proton-Translocating ATPases