Mitochondrial Sources of ROS in Cardio Protection and Ischemia/Reperfusion Injury

Several lines of evidence suggest that the reactive oxygen species (ROS) generatated by mitochondria have a pivotal role in determining activation of cardioprotective pathways and cell survival or, alternatively, in damaging cellular components and initiating cell death. In this article, we report the role of some important components of mitochondria in determining protective ROS signaling or deleterious ROS stress. We discuss studies showing the mechanisms whereby ROS generation occurs in pre (PreC) and postconditioning (PostC) and myocardial ischemia/ reperfusion (I/R) injury. In particular, we consider mitochondrial ROS production that target respiratory complexes, mitochondrial ATP-sensitive potassium (mKATP) channels or connexin 43 (Cx43) to activate cell survival programs, in conditioning by ischemic and pharmacologic agents. ROS signaling renders cells more resistant to the detrimental effects of I/R, via activation of enzymes and limitation of mitochondrial permeability transition pore (mPTP) opening. Importantly, this pore plays a crucial role in determining ROS production and cell death. Moreover, we consider the role of other mitochondrial components which mainly contribute to deleterious ROS generation, namely monoamine oxidase (MAO) and growth factor adaptor Shc (p66Shc), which may interact with other components to generate ROS and may be the putative target(s) of therapeutic agents.