LAUSR

In the heart, rigorous regulation of intracellular calcium levels is integral to maintain cell survival and cardiac homeostasis. Calcium is a highly versatile signaling molecule that is involved in regulating many diverse processes, ranging from mitochondrial metabolism to cardiac contraction. Mitochondria are known to take up calcium, and many mitochondrial enzymes in the tricarboxylic acid cycle are calcium-dependent.1 However, calcium also has a dark side where excess uptake can lead to destruction of mitochondria and activation of necrotic cell death.2 Mitochondrial calcium overload leads to opening of the mitochondrial permeability transition pore (mPTP), allowing for the influx of solutes and water into the matrix. This ultimately causes mitochondrial swelling and rupture with activation of necrotic cell death. Mitochondrial calcium overload and mPTP opening occur during myocardial ischemia/reperfusion (I/R) and are major contributors to the injury.2 Not surprisingly, both mitochondrial calcium influx and efflux are highly regulated processes and an increased understanding of the mechanisms regulating these events could provide important avenues for therapeutic intervention to limit I/R injury in patients.