Non-apoptotic roles of Bcl-2 family: the calcium connection.

The existence of the bcl-2 (B-cell lymphoma-2) gene was reported nearly 30 years ago. Yet, Bcl-2 family group of proteins still surprises us with their structural and functional diversity. Since the discovery of the Bcl-2 family of proteins as one of the main apoptosis judges, the precise mechanism of their action remains a hot topic of intensive scientific research and debates. Although extensive work has been performed on the role of mitochondria in apoptosis, more and more studies point out an implication of the endoplasmic reticulum in this process. Interestingly, Bcl-2 family proteins could be localized to both the mitochondria and the endoplasmic reticulum highlighting their crucial role in apoptosis control. In particular, in these organelles Bcl-2 proteins seem to be involved in calcium homeostasis regulation although the mechanisms underlying this function are still misunderstood. We now assume with high degree of certainty that the majority of Bcl-2 family members take part not only in apoptosis regulation but also in other processes important for the cell physiology briefly denominated as "non-apoptotic" functions. Drawing a complete and comprehensive image of Bcl-2 family requires the understanding of their implications in all cellular processes. Here, we review the current knowledge on the control of calcium homeostasis by the Bcl-2 family at the endoplasmic reticulum and at the mitochondria. Then we focus on the non-apoptotic functions of the Bcl-2 proteins in relation with the regulation of this versatile intracellular messenger. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.