Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations

Abstract

Rat heart mitochondrial membranes exposed to the free radicals generating system tert-butylhydroperoxide/Cu 2+ undergo lipid peroxidation as evidenced by the accumulation of thyobarbituric acid reactive substances. Mitochondrial lipid peroxidation resulted in a marked loss of both cytochrome c oxidase activity and cardiolipin content. The alterations in the properties of cytochrome c oxidase were confined to a decrease in the maximal activity (V m x ) with no change in the affinity (K m ) with respect to the substrate cytochrome c. Various lipid soluble antioxidants could prevent the lipid peroxidation reaction and the associated loss of cytochrome c oxidase activity. External added cardiolipin but no other phospholipids, nor peroxidized cardiolipin was able to prevent the loss of cytochrome oxidase activity induced by lipid peroxidation. These results establish a close correlation between oxidative damage to cardiolipin and alterations in the cytochrome oxidase activity and may prove useful in probing molecular mechanism of free radicals induced peroxidative damage of mitochondria which has been proposed to contribute to aging and to chronic degenerative diseases.z 1998 Federation of European Biochemical Societies.

Two subpopulations of mitochondria in the aging rat heart display heterogenous levels of oxidative stress

“…First, the previously reported lesions in Complex III are only present in the IFM [11,[27][28][29]. Because Complex III is one of the primary sites for electron leakage, its decline would likely result in heightened production of reactive oxygen species [11].…”

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

“…Moreover, cardiac CL deficiencies have been reported in several cardiac pathologies associated with mitochondrial respiratory dysfunction and have been linked specifically to decreased COx activity in hypothyroidism (55), aging (22), and free radical stress (56). Interestingly, Yamaoka-Koseki, Urade, and Kito (52) found that delipidated bovine COx activity was stimulated only by reconstitution with L 4 CL-enriched CL fractions, and not L 4 CL-deficient fractions.…”

Mitochondria: A mirror into cellular dysfunction in heart disease

“…Containing cardiolipin, a phospholipid essential for function [107], the decrease in activity of COX associated with I/R may be in response to hydrolysis [108] or lipid peroxidation of cardiolipin [109,110]. Specific to the subsarcolemmal mitochondria [111], the modification status of cardiolipin could be identified readily using numerous proteomic techniques, with high emphasis on mass spectrometric-based characterization.…”