[The protective effect of cyclosporine A, carnitine, and Mg(2+) with ADP during calcium(2+)-dependent permeabilization of mitochondria by fatty acids and activation of NADH oxidation by an external pathway]

Abstract

The ability of cyclosporin A, Mg2+ plus ADP and L-carnitine to enhance energy recoupling in liver mitochondria and to inhibit the induction of the external pathway of NADH oxidation during Ca(2+)-dependent oxidative phosphorylation uncoupling by palmitate has been studied. Cyclosporin A, Mg2+ plus ADP and L-carnitine plus ATP prevent with an equal efficiency the induction of the external pathway of NADH oxidation by palmitate and Ca2+ in mitochondria but differ drastically by their ability to increase the coupling in permeabilized mitochondria. The recoupling effect of cyclosporin is manifested after addition of Mg2+ plus ADP. The protective action of Mg2+ plus ADP is prevented by preincubation with carboxyatractylate. Oxidation of NADH via an external pathway results in delta psi generation, however, only in the presence of the recoupling factors. The role of the cyclosporin-sensitive pore in Ca(2+)-dependent damage of mitochondria as well as in the induction of the external pathway of NADH oxidation is discussed.