RELATIONS BETWEEN TOCOPHEROL DEPLETION AND COENZYME-Q DURING LIPID-PEROXIDATION IN RAT-LIVER MITOCHONDRIA

In order to evaluate different mitochondrial antioxidant systems, the depletion of alpha-tocopherol and the levels of the reduced and oxidiz ed forms of CoQ were measured in rat liver mitochondria during Fe++/as corbate and NADPH/ADP/Fe++ induced lipid peroxidation. During the indu ction phase of malondialdehyde formation, alpha-tocopherol declined mo derately to about 80% of initial contents, whereas the total CoQ pool remained nearly unchanged, but reduced CoQ9 continuously declined. At the start of massive malondialdehyde formation, CoQ9 reaches its fully oxidized state. At the same time alpha-tocopherol starts to decline s teeply, but never becomes fully exhausted in both experimental systems . Evidently the oxidation of the CoQ9 pool constitutes a prerequisite for the onset of massive lipid peroxidation in mitochondria and for th e subsequent depletion of alpha-tocopherol. Trapping of the GSH by add ition of dinitrochlorbenzene (a substrate of the GSH transferase), res ults in a moderate acceleration of lipid peroxidation, but alpha-tocop herol and ubiquinol levels remained unchanged when compared with the c ontrols. Addition of succinate to GSH depleted mitochondria effectivel y suppressed MDA formation as well as alpha-tocopherol and ubiquinol d epletion. The data support the assumption that the protective effect o f respiratory substrates against lipid peroxidation in the absence of mitochondrial GSH is mediated by the regeneration of the lipid soluble antioxidants CoQ and alpha-tocopherol.