PEROXIDATIVE DAMAGE TO CARDIAC MITOCHONDRIA - CYTOCHROME-OXIDASE AND CARDIOLIPIN ALTERATIONS

Rat heart mitochondrial membranes exposed to the free radicals generat ing system tert-butylhydroperoxide/Cu2+ undergo lipid peroxidation as evidenced by the accumulation of thyobarbituric acid reactive substanc es. Mitochondrial lipid peroxidation resulted in a marked loss of both cytochrome c oxidase activity and cardiolipin content. The alteration s in the properties of cytochrome c oxidase were confined to a decreas e in the maximal activity (V-max) with no change in the affinity (K-m) with respect to the substrate cytochrome c. Various lipid soluble ant ioxidants could prevent the lipid peroxidation reaction and the associ ated loss of cytochrome c oxidase activity. External added cardiolipin but no other phospholipids, nor peroxidized cardiolipin was able to p revent the loss of cytochrome oxidase activity induced by lipid peroxi dation. These results establish a dose correlation between oxidative d amage to cardiolipin and alterations in the cytochrome oxidase activit y and map prove useful in probing molecular mechanism of free radicals induced peroxidative damage of mitochondria which has been proposed t o contribute to aging and to chronic degenerative diseases. (C) 1998 F ederation of European Biochemical Societies.