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

Abstract

Mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) 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 mitoK(ATP) opening reduces reactive oxygen species generation in heart, liver and brain mitochondria. Decreased H(2)O(2) release is observed when mitoK(ATP) is active both with respiration stimulated by oxidative phosphorylation and when ATP synthesis is inhibited. In addition, decreased H(2)O(2) release is observed when mitochondrial Delta pH 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.