Mitochondrial substrate oxidation-dependent protection against lipid peroxidation.

The effect of mitochondrial substrate oxidation on the NADPH-dependent lipid peroxidation of intact mitochondria, microsomes and of homogenate from rat liver was studied. It was found that addition of either succinate or beta-OH-butyrate decreased the rate of malondialdehyde production of mitochondria. The effect of succinate was found to be marked (80-90% inhibition). Addition of succinate strongly inhibited the lipid peroxidation of a reconstituted system containing both mitochondria and microsomes. Increasing the amount of mitochondria in this system resulted in enhancement of the inhibition. The same succinate effect on malondialdehyde formation in liver homogenate was also observed. These findings suggest that mitochondria supplied with respiratory substrates may play a role in the protection against the lipid peroxidation in the liver cell.