2009年02月26日

Apoptosis : Stabbed in the BAX

Apoptptic cell death is an intricate and highly regulated process. To isitiate apoptosis, the protein BIM binds to a hitherto unrecognized site on the BAX protain to trigger permeabilization of the outer mitochondrial membrane.

Cell death in animals mainly proceeds throuth the programmed prosess of apoptosis. In vertebrates, this usually occurs by means of pathway involving the mitochondrion, a cellular organelle (Green,D.R. Cell 121,671-674/2005).

Following damaging callular stress, the outer mitochondrial membrane becomes permeable, and factrors are released into the sytoplasm that precipitate apoptosis. the pro-apoptotic effector proteins of the BCL-2 family - BAK and BAX are responsible for permeabilizing the membrene, yet there is little structural information on the main protain-protein interactions necessary to promote this mitochondrial event. On page 1076 of this issue, Walensky, Tjandra and calleagues present an ontriguing structural analysis of the interactions between BAX and one of its activators, reavealing an unsuspected binding site.

Proteins of the BCL-2family control the integrity of the outer mitocondrial membrane and are divided into three subfamilies : anti-apoptotic proteins, pro-apoptotic effectors and BH3-only proteins (so called because, of the for evolutinarily conserved BCL-2-homology(BH)domains, only BH3 is present in these proteins).

Anti-apoptotic BCL-2 proteins prevent apoptosis by inhibiting permerbilization of the membrene, whereas the BH3-only proteins promote it.

When BAK and BAK are activated, they 'homo-oligomerize' - that is, they from complexes of either BAX-only or BAK-only molecules.

These olgomers assemble in the outer mitochondrial membrene, cousing its disruption. proteins localized between the outer and inner nenbreans, such as cytochrome ι,can then diffuse into the cytosol. Cytochrome ιand other released proteins cooperate with cytosolic factors, leading to the activation of caspase enzymes that are responsible for the features of apoptosis. But even without caspase activation, permeabilzed outer mitochondrial membrances can be sufficiently catasrophic to couse cell death.

The BH3-only protenis promote permeabilization ofthe outer mitochondrial membrane by regulating the other two subfamilies.


### DataBace ###
nature Vol.455 1007-1148 Issue no.7216 23 October 2008
News and Vews p.1047/ Apoptosis : Stabbed in the BAX / Douglas R. Green and Jerry E. Chipuk
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