Mitochondrial calcium in cardiac ischemia/reperfusion injury and cardioprotection

Abstract Mitochondrial calcium (Ca 2+ ) signals play a central role in cardiac homeostasis and disease. In the healthy heart, mitochondrial Ca 2+ levels modulate the rate of oxidative metabolism to match the rate of adenosine triphosphate consumption in the cytosol. During ischemia/reperfusion (I/R) injury, pathologically high levels of Ca 2+ in the mitochondrial matrix trigger the opening of the mitochondrial permeability transition pore, which releases solutes and small proteins from the matrix, causing mitochondrial swelling and ultimately leading to cell death. Pharmacological and genetic approaches to tune mitochondrial Ca 2+ handling by regulating the activity of the main Ca 2+ influx and efflux pathways, i.e., the mitochondrial Ca 2+ uniporter and sodium/Ca 2+ exchanger, represent promising therapeutic strategies to protect the heart from I/R injury.