INVOLVEMENT OF THE ADP ATP CARRIER IN PERMEABILIZATION PROCESSES OF THE INNER MITOCHONDRIAL-MEMBRANE/

The effect of different agents on inner-mitochondrial-membrane permeab ilization and lipoperoxidation induced by Ca2+ and the pyridine-nucleo tide oxidant t-butylhydroperoxide or inorganic phosphate was investiga ted. Comparing the protection conferred by ADP, a substrate of the ADP /ATP carrier, dithiothreitol, a disulfide reductant and butylhydroxyto luene, a radical scavenger, it was found that ADP was always the most effective against mitochondrial damage, when present in the incubation medium from the beginning. Moreover, carboxyatractyloside, a specific inhibitor of the ADP/ATP carrier, abolished completely the protective effect of ADP on both the lipoperoxidation and mitochondrial swelling processes. Experiments where deenergized mitochondria were previously incubated with Ca2+ showed a decrease in the content of active ADP/AT P carrier, indicating a direct involvement of this protein in the form ation of a non-specific Ca2+-dependent pore. Our results also eliminat e the possibility of an attack of oxygen radicals on lipids or protein s of the mitochondrial membrane as the primary event triggering the pe rmeability transition of the inner mitochondrial membrane.