The effects of phosphate and electron transport on the carbonyl cyanide m-chlorophenylhydrazone-induced ATPase of rat-liver mitochondria.
1. The effects of phosphate and electron transport on the ATPase induced in rat-liver mitochondria by the uncoupler carbonyl cyanide m-chlorophenylhydrazone have been measured at different uncoupler concentrations and compared with those of ATP, oligomycin and aurovertin. 2. The inhibitory action of respiratory-chain inhibitors on the ATPase activity, which is independent of the actual inhibitor used, is greatly delayed or prevented by the presence of uncoupler, and, in the case of rotenone, can be reversed completely by the subsequent addition of succinate (in the absence of uncoupler). These results can be explained on the basis of the proposal previously made by others that coupled electron transfer causes a structural change in the ATPase complex that results in a decreased affinity of the ATPase inhibitor for the mitochondrial ATPase. 3. Inorganic phosphate specifically stimulates the ATPase activity at high uncoupler concentrations (greater than 0.2 muM), but has no effect at low concentrations. The stimulation is prevented or abolished by sufficiently high concentrations of aurovertin. 4. Aurovertin prevents the inhibition of the uncoupler-induced ATPase by high uncoupler concentrations. 5. It is proposed that the steady-state concentration of endogenous P-i may be an important regulator of the turnover of the ATPase in intact mitochondria and that the inhibition of ATPase activity by high concentrations of uncoupler is at least partially mediated via changes in the concentration of endogenous P-i.
D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology*; D009840:Oligomycins / Q000494:pharmacology; D009994:Osmolar Concentration; D010710:Phosphates / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012402:Rotenone / Q000494:pharmacology
D000963:Antimetabolites; D003486:Cyanides; D006835:Hydrazones; D009570:Nitriles; D009840:Oligomycins; D010710:Phosphates; D012402:Rotenone; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases