Mitochondrial Apoptosis Regulation by Bcl-2 Family Members

A key ampLificatory mechanism of programmed cell death depends on the release of proapoptotic factors from the mitochondria, crucial organelles in intermediary metaboLism, and energy conversion characterized by a dynamic morphology, ultrastructure, and intracellular locaLization. The proapoptotic factor required for the assembly of the apoptosome and hence for the activation of effector caspases is the only soluble component of the mitochondrial electron transport chain, cytochrome c, whose submitochondrial locaLization is controlled by the organellar shape. Its release across the outer mitochondrial membrane is controlled by the cell death regulator proteins that belong to the family of B cell lymphoma (BCL)-2, the first oncogene to be discovered to function in the regulation of apoptosis. In this article, we will summarize how Bcl-2 family members recruit mitochondria in the apoptotic pathway, by causing their permeabiLization and morphological remodeLing.