Inhibition of the adenine nucleotide translocator by matrix-localized palmityl-CoA in rat heart mitochondria.
The activity of the adenine nucleotide translocator in rat heart mitochondria was quantitatively determined by the rate of [14C]ATP transport at 2 degrees C using the carboxyatractyloside inhibitor-stop technique. Linear uptake was obtained for 15 s, and with differing protein concentrations. The effect of matrix long-chain acyl-CoA esters upon the adenine nucleotide translocator activity was determined in these mitochondria. Incubation with palmitylcarnitine produced an increase in matrix long-chain acyl-CoA esters and decreased the velocity of [14C]ATP transport. Mitochondria isolated in the presence of KCN showed elevated levels of long-chain acyl-CoA esters, decreased transportable nucleotides, and very low adenine nucleotide translocator activity. Addition of potassium ferricyanide to these mitochondria caused a reduction in matrix acyl-CoA esters and partially restored adenine nucleotide translocator activity. Potassium ferricyanide also lowered matrix acyl-CoA in freshly isolated mitochondria and increased [14C]ATP transport. These findings show that the level of long-chain acyl-CoA esters within the mitochondrial matrix affects adenine nucleotide translocator activity and regulates mitochondrial activity.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D010172:Palmitoylcarnitine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D000214:Acyl Coenzyme A; D010171:Palmitoyl Coenzyme A; D010172:Palmitoylcarnitine; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D009713:Nucleotidyltransferases