MITOCHONDRIAL RESPIRATION SCAVENGES EXTRAMITOCHONDRIAL SUPEROXIDE ANION VIA A NONENZYMATIC MECHANISM

We determined that mitochondrial respiration reduced cytosolic oxidant stress in vivo and scavenged extramitochondrial superoxide anion (O .(-)(2)) in vitro, First, Saccharomyces cerevisiae deficient in both the cytosolic antioxidant cupro-zinc superoxide dismutase (Cu,Zn-SOD) and electron transport (Rho(O) state) grew poorly (P < 0.05) in 21% O-2 compared with parent yeast and yeast deficient only in electron transport or Cu,Zn-SOD, whereas anaerobic growth was the same (P > 0.05) in all yeast, Second, isolated yeast and mammalian mitochondria scavenged extramitochondrial O .(-)(2) generated by xanthine/xanthine oxidase, Yeast mitochondria scavenged 42% more (P < 0.05) extramitochondrial O .(-)(2) during pyruvate/malate-induced respiration than in the resting state, Addition of either antimycin (respiratory chain inhibitor) or FCCP (respiratory chain uncoupler) prevented increased O .(-)(2) scavenging, Mitochondria isolated from yeast deficient in the mitochondrial manganous superoxide dismutase (Mn-SOD) increased (P < 0.05) O .(-)(2) scavenging 56% during respiration, This apparent SOD activity, expressed in units of SOD activity per milligram of mitochondrial protein, was the same (9 +/- 0.6 vs. 10 +/- 1.0; P = 0.43) as the O .(-)(2) scavenging of mitochondria with Mn-SOD, suggesting that respiration-dependent mitochondrial O .(-)(2) scavenging was nonenzymatic, Finally, isolated rat liver and lung mitochondria also increased (P < 0.05) O .(-)(2) scavenging during respiration, We speculate that respiring mitochondria, via the protonmotive pump, present a polarized, proton-rich surface that enhances nonenzymatic dismutation of extramitochondrial O .(-)(2) and that this is a previously unrecognized function of mitochondrial respiration with potential physiological ramifications.