Protein Kinases and Regulation of Mitochondrial Function in Ischemia/Reperfusion Injury

Ischemic heart disease and stroke are the leading causes of death worldwide. Nonetheless, our understanding of the molecular mechanisms regulating cardiac and cerebral ischemic injury is very modest and our ability to develop therapies arresting and/or reversing detrimental events that spread from the ischemic core to the surrounding tissue is limited. Ischemia occurs when oxygen is unavailable to tissues due to occlusion of an artery (myocardial infarction, stroke, and pulmonary embolism), hemorrhage, organ transplantation, or hypotension in septic shock. The mitochondrion is a key target of ischemia. Alterations in mitochondrial morphology, dynamics, and functions result in energy deficits and contribute to the pathogenesis of ischemic injury. Phosphorylations of mitochondrial proteins and protein kinases that mediate them are important regulators of mitochondrial functions and tissue ATP levels. Thus, mitochondrial protein kinases could serve as targets for therapeutic interventions to mitigate the effects of ischemic injury. This will review the mitochondrial proteins regulated by phosphorylation, protein kinases mediating these reactions, and their implications in mitochondrial functions in ischemia/reperfusion (I/R)-induced injury.