Mitochondria in Ischemic Heart Disease

Abstract

A core feature of ischemic heart disease is injury to cardiomyocytes (CMC). Ischemic CMC manifest the molecular mechanisms to undergo the major forms of cell injury and death, namely, oncotic necrosis, necroptosis, apoptosis and unregulated autophagy. Important modulators of ischemic injury are reperfusion and conditioning. Mitochondria have a major role in mediating the injury to CMC through membrane protein complexes referred to as death channels. Apoptosis is mediated by activation of a channel regulated by the Bcl-2 protein family leading to mitochondrial outer membrane permeabilization (MOMP). Oncotic type injury is mediated by opening of the mitochondrial permeability transition pore (mPTP). Mitochondria also have a reperfusion salvage kinase pathway (RISK). With cyclosporine A serving as a prototype, ongoing research is aimed at developing pharmacological approaches to condition and preserve mitochondrial integrity in order to promote CMC survival during episodes of myocardial ischemia.

Keywords: Cardiomyocytes; Conditioning; Mitochondria; Mitochondrial outer membrane permeabilization (MOMP); Mitochondrial permeability transition pore (mPTP); Myocardial ischemia; Reperfusion.