Oct 6, 2007

High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates

The Biochemical Journal
Florian L MullerHolly Van Remmen

Abstract

Despite the considerable interest in superoxide as a potential cause of pathology, the mechanisms of its deleterious production by mitochondria remain poorly understood. Previous studies in purified mitochondria have found that the highest rates of superoxide production are observed with succinate-driven reverse-electron transfer through complex I, although the physiological importance of this pathway is disputed because it necessitates high concentrations of succinate and is thought not to occur when NAD is in the reduced state. However, very few studies have examined the rates of superoxide production with mitochondria respiring on both NADH-linked (e.g. glutamate) and complex II-linked substrates. In the present study, we find that the rates of superoxide production (measured indirectly as H2O2) with glutamate+succinate (approximately 1100 pmol of H2O2 x min(-1) x mg(-1)) were unexpectedly much higher than with succinate (approximately 400 pmol of H2O2 x min(-1) x mg(-1)) or glutamate (approximately 80 pmol of H2O2 x min(-1) x mg(-1)) alone. Superoxide production with glutamate+succinate remained high even at low substrate concentrations (<1 mM), was decreased by rotenone and was completely eliminated by FCCP (carbonyl cyani...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Hydrogen Peroxide
Oxaloacetates
Rotenone
Alpha Ketoglutarate
Pyruvate Measurement
Electron Transport
Succinates
Oxaloacetate

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