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lüll High- and low-calcium-dependent mechanisms of mitochondrial calcium signalling Spat A; Szanda G; Csordas G; Hajnoczky GCell Calcium 2008[Jul]; 44 (1): 51-63The Ca(2+) coupling between endoplasmic reticulum (ER) and mitochondria is central to multiple cell survival and cell death mechanisms. Cytoplasmic [Ca(2+)] ([Ca(2+)](c)) spikes and oscillations produced by ER Ca(2+) release are effectively delivered to the mitochondria. Propagation of [Ca(2+)](c) signals to the mitochondria requires the passage of Ca(2+) 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 Ca(2+) between the ER membrane and OMM. In this setting, even >100 microM [Ca(2+)] may be attained to activate the low affinity mitochondrial Ca(2+) uptake. However, a mitochondrial [Ca(2+)] rise has also been documented during submicromolar [Ca(2+)](c) elevations. Evidence has been emerging that Ca(2+) exerts allosteric control on the Ca(2+) transport sites at each membrane, providing mechanisms that may facilitate the Ca(2+) delivery to the mitochondria. Here we discuss the fundamental mechanisms of ER and mitochondrial Ca(2+) transport, particularly the control of their activity by Ca(2+) and evaluate both high- and low-[Ca(2+)]-activated mitochondrial calcium signals in the context of cell physiology.|*Mitochondria/genetics/metabolism[MESH]|Allosteric Regulation/genetics[MESH]|Animals[MESH]|Calcium Signaling/*physiology[MESH]|Calcium/*metabolism[MESH]|Cytoskeleton/physiology[MESH]|Endoplasmic Reticulum/genetics/*metabolism[MESH]|Humans[MESH]|Inositol 1,4,5-Trisphosphate Receptors/chemistry/genetics/*metabolism[MESH]|Mitochondrial Membrane Transport Proteins/metabolism[MESH]|Mitochondrial Membranes/physiology[MESH]|Mitochondrial Permeability Transition Pore[MESH]|Ryanodine Receptor Calcium Release Channel/genetics/*metabolism[MESH] |