PROTECTIVE EFFECT OF CYCLOSPORINE-A, CARNITINE, AND MG2-DEPENDENT PERMEABILIZATION OF MITOCHONDRIA BY FATTY-ACIDS AND DURING ACTIVATION OF NADH OXIDATION VIA AN EXTERNAL PATHWAY( PLUS ADP DURING CA2+)

The ability of cyclosporin A, Mg2+ plus ADP, and L-carnitine to enhanc e energy recoupling in liver mitochondria and to inhibit the induction of the external pathway of NADH oxidation during Ca2+-dependent uncou pling of oxidative phosphorylation by palmitate has been studied Cyclo sporin A, Mg2+ plus ADP, and L-carnitine plus ATP prevent with equal e fficiency the external pathway of NADH oxidation by palmitare and Ca2 in mitochondria but differ drastically in their ability to increase t he coupling in permeabilized mitochondria. The recoupling effect of cy closporin is manifested after addition of Mg2+ plus ADP. The protectiv e action of Mg2+ plus ADP is prevented by preincubation with carboxyat ractylate. Oxidation of NADH via the external pathway results in Delta Psi generation, but only in the presence of recoupling factors. The r ole of a cyclosporin-sensitive pore in Ca2+-dependent damage to mitoch ondria as well as in the induction of the external pathway of NADH oxi dation is discussed.