Regulation of the mitochondrial ATPase in situ in cardiac muscle: role of the inhibitor subunit.
The mitochondrial F1-ATPase inhibitor protein, IF1, binds to beta subunits of the F1-ATPase both in vitro and in situ under nonenergizing conditions, i.e., under conditions that allow a net hydrolysis of ATP by the mitochondrial ATPase to take place. This reversible IF1 binding occurs in a wide variety of cell types including (anaerobic) baker's yeast cells and (ischemic) mammalian cardiomyocytes under conditions that limit oxidative phosphorylation. The binding of inhibitor results in a marked slowing of ATP hydrolysis by the undriven mitochondrial ATP synthase. An apparent main function of this reversible IF1 binding, at least in cells that undergo aerobic-anaerobic switching, is the mitigation of a wasteful hydrolysis of ATP produced by glycolysis during anoxic or ischemic intervals, by the mitochondrial ATPase. While this apparent main function is probably of considerable importance in cells that normally either can or must undergo aerobic-anaerobic switching such as baker's yeast cells and skeletal myocytes, one wonders why a full complement of IF1 has been retained in certain cells that normally do not undergo such aerobic-anaerobic switching, cells such as adult mammalian cardiomyocytes of many species. While some mammalian species have, indeed, not retained a functional complement of IF1 in their cardiomyocytes, those that have can benefit significantly from its presence during intervals of myocardial ischemia.
Rouslin
W
W
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*; D000097795:ATPase Inhibitory Protein
D000251:Adenosine Triphosphatases; D011506:Proteins; D000097795:ATPase Inhibitory Protein