The Destruction of Cytochrome c in a Complex with Cardiolipin during Catalysis of Lipid Peroxidation

摘要

The destruction of cytochrome c during its catalysis of the lipoperoxidase reaction, which causes the impairment of mitochondrial membranes in living cells and the release of various pro-apoptotic factors into the cytosol, was studied. Spectrophotometric analysis showed a much more intense destruction of cytochrome c when hydrogen peroxide was added in the presence of tetraoleylcardiolipin at protein : cardiolipin ratios of 1 : 30 and 1 : 60, which were optimal for the formation of a cytochrome c complex with cardiolipin, compared to the sample in which only hydrogen peroxide and cytochrome c were present. In the second case, the destruction of the porphyrite group of heme took the form of a linear function, while in the presence of cardiolipin the dependence was clearly exponential; upon addition of a lipid substrate, phosphatidic acid, the value of the first-order rate constant of the cytochrome c destruction increased. It is proposed that the rapid destruction of cytochrome c during its catalysis of the lipoperoxidase reaction is an evolutionarily developed mechanism for preventing the spontaneous initiation of apoptosis.