Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles

Bcl-2 family proteins are considered as one of the major regulators of apoptosis. Indeed, this family is known to control the mitochondrial outer membrane permeabilization (MOMP): a central step in the mitochondrial pathway of apoptosis. However, in recent years Bcl-2 family members began to emerge as a new class of intracellular calcium (Ca(2+)) regulators. At mitochondria-ER contacts (MERCs) these proteins are able to interact with major Ca(2+) transporters, thus controlling mitochondrial Ca(2+) homeostasis and downstream Ca(2+) signalling pathways. Beyond the regulation of cell survival, this Bcl-2-dependent control over the mitochondrial Ca(2+) dynamics has far-reaching consequences on the physiology of the cell. Here, we review how the Bcl-2 family of proteins mechanistically regulate mitochondrial Ca(2+) homeostasis and how this regulation orchestrates cell death/survival decisions as well as the non-apoptotic process of cell migration.