Bax: Addressed to kill

The pro-apoptototic protein Bax (Bcl-2 Associated protein X) plays a central role in the mitochondria-dependent apoptotic pathway. In healthy mammalian cells, Bax is essentially cytosolic and inactive. Following a death signal, the protein is translocated to the outer mitochondrial membrane, where it promotes a permeabilization that favors the release of different apoptogenic factors, such as cytochrome c. The regulation of Bax translocation is associated to conformational changes that are under the control of different factors. The evidences showing the involvement of different Bax domains in its mitochondrial localization are presented. The interactions between Bax and its different partners are described in relation to their ability to promote (or prevent) Bax conformational changes leading to mitochondrial addressing and to the acquisition of the capacity to permeabilize the outer mitochondrial membrane.

► Molecular mechanisms governing Bax mitochondrial addressing are reviewed.
► Both the N- and C-terminal ends of Bax regulate its mitochondrial localization.
► The receptor Tom22 is involved in optimal Bax addressing.
► Survival and death kinases directly regulate Bax conformational changes.
► Other Bcl-2 family members actively participate to Bax translocation.