LIPID-PEROXIDATION AND CHANGES IN THE UBIQUINONE CONTENT AND THE RESPIRATORY-CHAIN ENZYMES OF SUBMITOCHONDRIAL PARTICLES

The relationship between lipid peroxidation induced by ascorbate and a denosine ADP/Fe3+, and its effect on the respiratory chain activities of beef heart submitochondrial particles has been investigated. Lipid peroxidation, measured as thiobarbituric acid reactive substance forma tion, resulted in an inhibition of the NADH and succinate oxidase acti vities. Examination of several partial reactions of the respiratory ch ain revealed inactivation primarily of those involving endogenous ubiq uinone, i.e., NADH- and succinate-ubiquinone(1) and cytochrome c reduc tases. Ubiquinol-cytochrome c reductase, measured with reduced ubiquin one(2) as electron donor, was unaffected. The amount of NADH- or succi nate-reducible cytochrome b in the presence of cyanide was strongly de creased, but could be recovered by the addition of antimycin. There oc curred a substantial decrease of the ubiquinone content in the course of lipid peroxidation, with a linear relationship between this decreas e and the NADH and succinate oxidase activities. The results are consi stent with the conclusion that the ubiquinone pool undergoes an oxidat ive modification during lipid peroxidation, to a form that can no long er function as a component of the respiratory chain. Lipid peroxidatio n also led to a partial inhibition of the succinate d-hydrogenase and cytochrome c oxidase activities and a minor decrease of the cytochrome c and cytochrome a contents. Reduction of endogenous ubiquinone preve nted lipid peroxidation as well as the concomitant modification of ubi quinone and inactivation of the respiratory chain. These observations suggest that the destruction of ubiquinone through lipid peroxidation is the primary cause of inactivation of the respiratory chain, and emp hasize the antioxidant role of ubiquinol in preventing these effects. The possible implications of these findings for regulation of the cell ular turnover of ubiquinone by the prevailing oxidative stress are dis cussed. Copyright (C) 1996 Elsevier Science Inc.