The adenine nucleotide transport system of the inner membrane of rat liver mitochondria can be demonstrated to be specifically inhibited by oleyl CoA generated on the outer membrane from oleate plus CoA. This conclusion is supported by a number of observations including experiments conducted with rat liver mitochondria resolved of the long-chain fatty acid-CoA synthetase activity of the outer membrane by proteolytic digestion with Nagarse. The ATP-32Pi exchange activity of intact mitochondria was markedly inhibited by oleyl CoA, whereas this activity with submitochondrial particles (ETPH) was relatively insensitive. Likewise, the inorganic phosphate transport system of intact mitochondria was not found sensitive to oleyl CoA. Inhibition of the dinitrophenol-stimulated adenosine triphosphatase activity of intact mitochondria by oleyl CoA (or oleate in the presence of CoA) was found to be competitive with respect to ATP. Inhibition by oleate without added CoA was not competitive. Exogenous CoA also decreased the lag time needed for inhibition of the adenine nucleotide transport system by bongkrekic acid. This effect of CoA was abolished by inactivation of the long-chain fatty acid-CoA synthetase activity of the outer membrane. The results suggest that inhibition of the adenine nucleotide transport system by fatty acids and bongkrekic acid may be a function of formation of the CoA esters. However, the possibility that the unesterified acids are also inhibitory has not been excluded.
ASJC Scopus subject areas
- Molecular Biology