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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Cattle
  • Liposomes / metabolism
  • Mitochondrial Membranes / metabolism*
  • bcl-2-Associated X Protein / metabolism*


  • BH3 Interacting Domain Death Agonist Protein
  • Liposomes
  • bcl-2-Associated X Protein