Participation of endoplasmic reticulum and mitochondrial calcium handling in apoptosis: more than just neighborhood?

Over the past few years, extensive progress has been made in elucidating the role of calcium in the signaling of apoptosis. This has led to the characterization of calcium's role in the induction of apoptosis and in the regulation of effector proteases. In this review, we attempt to summarize the current knowledge regarding a segment of these studies, the interaction between the endoplasmic reticulum (ER) and mithochondria. This interface has been shown to play a crucial role in transferring agonist induced Ca2+ signals to mithochondria during physiological processes. Recent evidence, however, extended the role of this Ca2+ transfer to apoptotic pathways, showing that modulation of mithochondrial Ca2+ uptake from the ER side has a prominent role in modulating cellular fate. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.