Chapter 26 - Mitochondrial ROS production during ischemia-reperfusion injury

Abstract

Mitochondrial ROS have long been known to contribute to oxidative damage during ischemia-reperfusion (IR) injury in heart attack, stroke, and other pathological situations. Over the past few years, our work has suggested that ROS formation in IR injury was mainly coming from complex I. This led us to investigate the mechanism of the ROS production, and using a metabolomic approach, we found that the ROS production in IR injury came from the accumulation of succinate during ischemia that then drove mitochondrial ROS production by reverse electron transport at complex I during reperfusion. This surprising mechanism suggests further new therapeutic approaches to impact on the damage that mitochondrial ROS do in pathology. Here, we discuss our current understanding of how mitochondria produce ROS during IR injury.