Mechanisms of mitochondrial outer membrane permeabilization.

In response to many apoptotic stimuli, Bcl-2 family pro-apoptotic members, such as Bax and Bak, are activated. This results in their oligomerization, permeabilization of the outer mitochondrial membrane, and release of many proteins that are normally confined in the mitochondrial inter-membrane space. Among these proteins are cytochrome c, Smac/DIABLO, OMI/HtrA2, AIF and endonuclease G. Mitochondrial outer membrane permeabilization (MOMP) is also associated with fragmentation of the mitochondrial network. The mechanisms that lead to the oligomerization of proapoptotic members of the Bcl-2 family and to MOMP are still unclear and the role of mitochondrial fission in these events remains elusive.