Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation

Mitochondrial ATP-sensitive K+ channel (mitoKATP) opening was shown previously to slightly increase respiration and decrease the membrane potential by stimulating K+ cycling across the inner membrane. Here we show that mitoKATP opening reduces reactive oxygen species generation in heart, liver and brain mitochondria. Decreased H2O2 release is observed when mitoK(ATP) is active both with respiration stimulated by oxidative phosphorylation and when ATP synthesis is inhibited. In addition, decreased H2O2 release is observed when mitochondrial DeltapH is enhanced, an effect expected to occur when mitoK(ATP) is open. We conclude that mitoK(ATP) is an effective pathway to trigger mild uncoupling, preventing reactive oxygen species release. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.