Mechanism of mitochondrial membrane permealization during apoptosis

Mechanism of mitochondrial membrane permealization during apoptosis

The Bcl2 family proteins Bax and Bak are essential for the execution of many apoptotic programs. During apoptosis, Bax translocates to the mitochondria and mediates the permeabilization of the outer membrane, thereby facilitating the release of proapoptotic proteins. Yet the mechanistic details of the Baxinduced membrane permeabilization have so far remained elusive.

Two papers published in the journal EMBO J provide answers. They show that active Bax along with other proteins like Bax clustered into a broad distribution of distinct architectures, including full rings, as well as linear and arcshaped oligomeric assemblies that localized in discrete foci along mitochondria.

Remarkably, both rings and arcs assemblies of Bax perforated the membrane, as revealed by atomic force microscopy in lipid bilayers. The area enclosed by a Bax ring is devoid of mitochondrial outer membrane proteins such as Tom20, Tom22, and Sam50. This strongly supports the view that the Bax rings surround an opening required for mitochondrial outer membrane permeabilization (MOMP).

These studies identify the supramolecular organization of Bax during apoptosis and support a molecular mechanism in which Bax fully or partially delineates pores of different sizes to permeabilize the mitochondrial outer membrane.