Bcl-w(edding) with mitochondria

Trends Cell Biol. 2004 Jan;14(1):8-12. doi: 10.1016/j.tcb.2003.11.005.


Bcl-2-family members (Bcl-2, Bax, Bcl-w and Bcl-x(L)) are crucial integrators of signals for cell survival and death; the pro- or antiapoptotic activities of these proteins are regulated by their subcellular localization. Bcl-2 directly inserts into the membranes, where it acts; however, Bax requires a stimulus-dependent translocation from an inactive cytosolic to an active membrane-inserted state. Recently, a novel mechanism is described for the survival factor Bcl-w, which is active while weakly associated with mitochondria. In apoptotic cells, a BH3-only protein neutralizes the survival activity of Bcl-w by binding to its "hydrophobic pockets", thereby releasing its C-terminal domain and allowing its insertion into the membrane. Here, we discuss the importance of this finding for a better understanding of the action mode of Bcl-w and other Bcl-2-family members.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Humans
  • Membrane Proteins / physiology
  • Mitochondria / chemistry
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Proteins / analysis
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / physiology


  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2