ATPase complex and oxidative phosphorylation in chloramphenicol-induced megamitochondria from mouse liver.
1. Functional properties of the ATPase complex are investigated in megamitochondria isolated from livers of weanling mice fed a diet containing 2% chloramphenicol, as an inhibitor of mitochondrial protein synthesis. 2. Whereas the specific activity of ATPase remains unchanged in chloramphenicol-induced megamitochondria, about 40% of the enyzme activity is resistant to inhibition by oligomycin, triethyltin or venturicidin. It is concluded that the ATPase complex lacks one or more components whose synthesis or accumulation is dependent on mitochondrial translation. The inhibitor-resistant ATPase portion appears tightly bound to the mitochondrial membrane. 3. Respiratory chain phosphorylation is tightly coupled in isolated megamitochondria. ATP synthesis and ATP-Pi exchange are diminished by 40%, as compared to control mitochondria, but both processes are sensitive to oligomycin, triethyltin or venturicidin. 4. The decrease in ATP synthesis and ATP-Pi exchange in megamitochondria correlates quite well with the emergence of inhibitor-resistant ATPase. 5. The following electron transport activities in the megmitochondria are reduced: NADH-cytochrome c reductase, by 60%, cytochrome oxidase, by 80%; the amount of antimycin required to gain complete inhibition of the bc1-segment is diminished by more than 50%. On the other hand succinate dehydrogenase activity is increased by 50%. 6. Chloramphenicol-induced megamitochondria appear to be a useful system for studying the role of mitochondrial translation in the assembly of mammalian mitochondria.
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology; D003579:Cytochrome Reductases / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D012402:Rotenone / Q000494:pharmacology; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism
D003486:Cyanides; D012402:Rotenone; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002701:Chloramphenicol; D013384:Succinate Cytochrome c Oxidoreductase; D009247:NADH, NADPH Oxidoreductases; D003579:Cytochrome Reductases; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases