Are free radicals involved in Ca(2+)-induced membrane damage of mitochondria?

Ca(2+)-Induced membrane damage of energized mitochondria has been proposed to be due to lipid peroxidation induced by Ca2+. To examine this possibility, we studied the effects of the radical scavenger, 3,5-di-tert-butyl-4-hydroxytoluene (BHT), and its derivative, 3,5-di-tert-butyl-4-methoxytoluene (MeO-BHT), on membrane damage of respiring mitochondria induced by Ca2+ in the presence of inorganic phosphate. Both compounds inhibited Ca(2+)-induced damage almost completely at 20 microM, and their effects were identical, although MeO-BHT had no radical scavenging ability. These results indicate that the protective effects of BHT and MeO-BHT are not due to their radical scavenging ability. Thus, free radicals are concluded not to be involved in Ca(2+)-induced membrane damage of mitochondria.