Matsuzaki S, Szweda LI

Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.

Declines in the rate of mitochondrial electron transport and subsequent increases in the half-life of reduced components of the electron transport chain can stimulate O2*- formation. We have previously shown that, in solubilized cardiac mitochondria, Ca2+ mediates reversible free radical-induced inhibition of complex I. In the study presented here, submitochondrial particles prepared from rat heart were utilized to determine the effects of Ca2+ on specific components of the respiratory chain and on the rates of electron transport and O2*- production. The results indicate that complex I is inactivated when submitochondrial particles are treated with Ca2+. Inactivation was specific to complex I with no alterations in the activities of other electron transport chain complexes. Complex I inactivation by Ca2+ resulted in the reduction of NADH-supported electron transport activity. In contrast to the majority of electron transport chain inhibitors, Ca2+ suppressed the rate of O2*- production. In addition, while inhibition of complex III stimulated O2*- production, Ca2+ reduced the relative rate of O2*- production, consistent with the magnitude of complex I inhibition. Evidence indicates that complex I is the primary source of O2*- released from this preparation of submitochondrial particles. Ca2+ therefore inhibits electron transport upstream of site(s) of free radical production. This may represent a means of limiting O2*- production by a compromised electron transport chain.

Mesh Terms:
Animals, Calcium, Electron Transport, Electron Transport Complex I, Kinetics, Male, Mitochondria, Heart, Rats, Rats, Sprague-Dawley, Superoxides

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173793

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