Inhibition of complex I by Ca2+ reduces electron transport activity and the rate of superoxide anion production in cardiac submitochondrial particles.
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.
Matsuzaki
Satoshi
S
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Szweda
Luke I
LI
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors*
D013481:Superoxides; D042967:Electron Transport Complex I; D002118:Calcium