High- and low-calcium-dependent mechanisms of mitochondrial calcium signalling

The Ca2+ coupling between endoplasmic reticulum (ER) and mitochondria is central to multiple cell survival and cell death mechanisms. Cytoplasmic [Ca2+] ([Ca2+](c)) spikes and oscillations produced by ER Ca2+ release are effectively delivered to the mitochondria. Propagation of [Ca2+](c) signals to the mitochondria requires the passage of Ca2+ across three membranes, namely the ER membrane, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM). Strategic positioning of the mitochondria by cytoskeletal transport and interorganellar tethers provides a means to promote the local transfer of Ca2+ between the ER membrane and OMM. In this setting, even >100 mu M [Ca2+] may be attained to activate the tow affinity mitochondrial Ca2+. uptake. However, a mitochondrial [Ca2+] rise has also been documented during submicromolar [Ca2+](c) elevations. Evidence has been emerging that Ca2+ exerts allosteric control on the Ca2+ transport sites at each membrane, providing mechanisms that may facilitate the Ca2+ delivery to the mitochondria. Here we discuss the fundamental mechanisms of ER and mitochondrial Ca2+, transport, particularly the control of their activity by Ca2+ and evaluate both high- and low- [Ca2+] -activated mitochondrial calcium signals in the context of cell physiology. (c) 2007 Elsevier Ltd. All rights reserved.