Bcl-2 and Ca2+ homeostasis in the endoplasmic reticulum

Abstract

Recent data have revealed an unexpected role of Bcl-2 in modulating the steady-state levels and agonist-dependent fluxes of Ca2+ ions. Direct monitoring of endoplasmic reticulum (ER) Ca2+ concentration with recombinant probes reveals a lower state of filling in Bcl-2-overexpressing cells and a higher leak rate from the organelle. The broader set of indirect data using cytosolic probes reveals a more complex scenario, as in many cases no difference was detected in the Ca2+ content of the intracellular pools. At the same time, Ca2+ signals have been shown to affect important checkpoints of the apoptotic process, such as mitochondria, thus tuning the sensitivity of cells to various challenges. In this contribution, we will review (i) the data on the effect of Bcl-2 on [Ca2+]er, (ii) the functional significance of the Ca2+ - signalling alteration and (iii) the current insight into the possible mechanisms of this effect. © 2006 Nature Publishing Group. All rights reserved.