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lüll Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis Pinton P; Giorgi C; Siviero R; Zecchini E; Rizzuto ROncogene 2008[Oct]; 27 (50): 6407-18There is a growing consensus that the various forms of cell death (necrosis, apoptosis and autophagy) are not separated by strict boundaries, but rather share molecular effectors and signaling routes. Among the latter, a clear role is played by calcium (Ca(2+)), the ubiquitous second messenger involved in the control of a broad variety of physiological events. Fine tuning of intracellular Ca(2+) homeostasis by anti- and proapoptotic proteins shapes the Ca(2+) signal to which mitochondria and other cellular effectors are exposed, and hence the efficiency of various cell death inducers. Here, we will review: (i) the evidence linking calcium homeostasis to the regulation of apoptotic, and more recently autophagic cell death, (ii) the discussion of mitochondria as a critical, although not unique checkpoint and (iii) the molecular and functional elucidation of ER/mitochondria contacts, corresponding to the mitochondria-associated membrane (MAM) subfraction and proposed to be a specialized signaling microdomain.|Animals[MESH]|Apoptosis/*physiology[MESH]|Calcium/metabolism/*physiology[MESH]|Cytosol/metabolism[MESH]|Endoplasmic Reticulum/*metabolism[MESH]|Humans[MESH] |