Mitochondrial calcium handling during ischemia-induced cell death in neurons

Mitochondria sense and shape cytosolic Ca2+ signals by taking up and subsequently releasing Ca2+ ions during physiological and pathological Ca2+ elevations. Sustained elevations in the mitochondrial matrix Ca2+ concentration are increasingly recognized as a defining feature of the intracellular cascade of lethal events that occur in neurons during cerebral ischemia. Here, we review the recently identified transport proteins that mediate the fluxes of Ca2+ across mitochondria and discuss the implication of the permeability transition pore in decoding the abnormally sustained mitochondrial Ca2+ elevations that occur during cerebral ischemia.

► Mitochondria sequester Ca2+ ions during cellular Ca2+ signals.
► Increased matrix [Ca2+] might contribute to neurotoxicity during brain ischemia.
► Transport proteins that move Ca2+ ions into mitochondria have been identified.
► Excessive mitochondrial Ca2+ elevations might open the permeability transition pore.