Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection

Myocardial infarction is the leading cause of death in most industrialized nations throughout the world. High levels of oxygen radicals (ROS) in response to infarction (ischemia/reperfusion) are a major trigger of cardiomyocyte cell death, although their mode of action is only beginning to be understood. Here, we show that targeted disruption of a key mitochondrial ROS-detoxifying enzyme sensitizes to myocardial ischemia/reperfusion injury through opening of the mitochondrial transition pore. Importantly, pharmacological intervention, either through inhibition of the mitochondrial pore or by regeneration of the ROS-sensitive cellular thiol-pool, allowed restoring myocardial function and preventing tissue damage.