Send to

Choose Destination
Cell. 2008 Dec 12;135(6):1074-84. doi: 10.1016/j.cell.2008.11.010.

Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax.

Author information

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.


In normal circumstances, the Bcl-2 family dutifully governs when cells die. However, the rules of engagement between the pro- and antiapoptotic family members are still contested, and how Bax is transformed from a cytosolic monomer to an outer mitochondrial membrane-permeabilizing oligomer is unclear. With fluorescence techniques and an in vitro system, the combination of tBid and Bax produced dramatic membrane permeabilization. The membrane is not a passive partner in this process beause membranes are required for the protein-protein interactions to occur. Simultaneous measurements of these interactions revealed an ordered series of steps required for outer membrane permeabilization: (1) tBid rapidly binds to membranes, where (2) tBid interacts with Bax, causing (3) Bax insertion into membranes and (4) oligomerization, culminating in (5) membrane permeabilization. Bcl-XL prevents membrane-bound tBid from binding Bax. Bad releases tBid from Bcl-XL, restoring both tBid binding to Bax and membrane permeabilization.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center