INVOLVEMENT OF ASPARTATE GLUTAMATE ANTIPORTER IN FATTY ACID-INDUCED UNCOUPLING OF LIVER-MITOCHONDRIA/

Effects of aspartate, glutamate and an inhibitor of the aspartate/glut amate antiporter, diethylpyrocarbonate (DEPC), on uncoupling of the en ergy transduction processes in rat liver mitochondria have been invest igated. It is found that both the antiporter substrates and the antipo rter inhibitor operate as recouplers when uncoupling is caused by free fatty acids (FFA). Recoupling consists in (1) partial inhibition of t he FFA-stimulated respiration and (2) some increase in the membrane po tential. Half-maximal effects are observed at concentrations of glutam ate and aspartate close the K-m values of the antiporter. Recouplings by glutamate (aspartate) and DEPC are not additive. On the other hand, recoupling by any of these compounds and carboxyatractylate or ADP ap pears to be additive. Uncoupling by dinitrophenol is less sensitive to the recouplers whereas that by FCCP is not sensitive at all. It is co ncluded that uncoupling by FFA in rat liver mitochondria is mediated n ot only by the ATP/ADP antiporter but also by the aspartate/glutamate antiporter.