Permeabilization of the outer mitochondrial membrane by Bcl-2 proteins

The proteins of the Bcl-2 family regulate the release of the apoptotic factors from mitochondria during apoptosis, a key event in physiological cell death. Although their molecular mechanisms remain unclear, the Bcl-2 proteins have been proposed to directly control the permeability of the outer mitochondrial membrane by pore formation. Indeed, they share structural features with the pore forming domains of some bacterial toxins and they can give rise to proteolipidic pores in model membranes. The complex level of regulation needed to decide the fate of the cell is achieved by an intricate interaction network between different members of the family. Current models consider multiple parallel equilibria of activation and inhibition that determine whether the permeabilization of the mitochondrial outer membrane is induced or not.