Inhibition of oxidative phosphorylation by an oligomer of prostaglandin B1, PGBx.
PGBx is a synthetic, oligomeric derivative of prostaglandin B1 that has been shown to protect rat liver mitochondria from the deleterious effects of aging. In fresh mitochondria, PGBx inhibits reactions involving the F1F0-ATPase. It prevents the stimulation of respiration by ADP and inhibits ATP-driven Ca2+ transport. It has no effect, however, on Ca2+-stimulated respiration and associated proton movements, or on respiration-driven Ca2+ transport, indicating that PGBx is not an inhibitor of the electron transport chain. The ATPase activity of submitochondrial particles is inhibited by PGBx with mixed type kinetics in which both Km and V are affected. PGBx has no effect on the ATPase activity of soluble F1, but induces respiratory control in F1-deficient submitochondrial particles, indicating a mode of action similar to oligomycin and DCCD. The binding of DCCD to its proteolipid receptor is inhibited by PGBx, suggesting that this is the binding site for PGBx. It is concluded that PGBx inhibits reactions involving the F1F0-ATPase by binding at or near the DCCD-binding protein and blocking proton conduction through the F0 moiety of the complex.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000367:Age Factors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D011456:Prostaglandins B / Q000494:pharmacology*; D006180:Proton-Translocating ATPases; D051381:Rats; D011919:Rats, Inbred Strains
D011108:Polymers; D011453:Prostaglandins; D011456:Prostaglandins B; C024303:prostaglandin Bx; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D002118:Calcium