Mitochondrial Involvement in the Molecular Mechanisms of Ischemia-Reperfusion Injury in the Heart

Abstract

Mitochondria play a key role in maintaining cell viability and cellular basic functions by energy (ATP) production. These organelles are also considered as an important source of reactive oxygen species (ROS) and several apoptosis activators. The crucial role of mitochondria has been shown in numerous aspects of cell physiology and pathophysiology, such as intracellular signaling. Mitochondria and mitochondrial function may deteriorate under pathological conditions like various diseases, ischemia-reperfusion (IR) injury and during aging. Damaged or injured mitochondria are the main causes for cell and tissue impairments, due to various cell stresses, generation of excess of ROS  (oxidative stress), increased cellular and mitochondrial calcium levels, associated with apoptotic or/and necrotic cell death. The interplay among these mitochondrial activities under normal and pathological conditions is still unsuccessfully recognized. Mitochondria play a critical role in cardiac IR injury, where they are directly involved in various pathophysiological mechanisms. Here, we discuss the role of mitochondrial dynamics (fission, fusion) and heterogeneity. In particular, we stress the existence in the heart and skeletal muscles functionally different mitochondrial subpopulations that may also have different sensitivities to diseases and IR injury. Thus, different cardioprotective medications that maintain stability of mitochondria, their dynamics and turnover, including several agents, specific mitochondrial antioxidants, uncouplers, and application of ischemic preconditioning might be considered as the possible, beneficial strategies to protect mitochondria and cardiac function and improve longevity.