BH3-only proteins and their roles in programmed cell death

Oncogene. 2008 Dec;27 Suppl 1:S128-36. doi: 10.1038/onc.2009.50.


The Bcl-2 family of proteins controls the mitochondrial pathway to apoptosis. It consists of pro-survival and pro-apoptotic members, and their interactions decide whether apoptogenic factor confined to the mitochondrial intermembrane space can leak to the cytosol. Despite the intense efforts to understand the molecular mechanisms that lead to the permeabilization of the mitochondrial membrane, this particular issue remains a matter of intense controversy. It is well accepted that pro-apoptotic Bax and Bak are directly responsible for the damage to the mitochondria, but pro-survival family members prevent them from doing so. It is also accepted that stress signals activate selected Bcl-2 homology (BH)3-only proteins. But do these BH3-only proteins bind and activate Bax and Bak directly, or do they inhibit the pro-survival family members?

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Survival / physiology
  • Embryonic Development / physiology
  • Humans
  • Mice
  • Mice, Knockout
  • Mitochondria / physiology
  • Mitochondrial Membranes / metabolism
  • Models, Biological
  • Multigene Family
  • Permeability
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / classification
  • Proto-Oncogene Proteins c-bcl-2 / physiology*


  • Proto-Oncogene Proteins c-bcl-2