Mitochondrial calcium in cardiac ischemia/reperfusion injury and cardioprotection.

Abstract

Mitochondrial calcium (Ca²⁺) signals play a central role in cardiac homeostasis and disease. In the healthy heart, mitochondrial Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ handling by regulating the activity of the main Ca²⁺ influx and efflux pathways, i.e., the mitochondrial Ca²⁺ uniporter and sodium/Ca²⁺ exchanger, represent promising therapeutic strategies to protect the heart from I/R injury.