BH3-only proteins trigger cytochrome c release, but how?

Arch Biochem Biophys. 2007 Jun 15;462(2):150-5. doi: 10.1016/ Epub 2007 Jan 9.


The mitochondrial apoptosis pathway has been neatly ordered. Mitochondrial apoptosis is governed by Bcl-2 family proteins, and their respective contributions determine the release of cytochrome c. It is clear that, among the Bcl-2 family, BH3-only proteins are the triggers: activation of BH3-only proteins by apoptotic stimuli initiates the process. BH3-only proteins cause cytochrome c release by activating Bax and/or Bak, and the anti-apoptotic group of Bcl-2-like proteins prevents this. However, it is curiously uncertain how BH3-only proteins activate Bax/Bak. Current models suggest that this is either through direct interaction--although this interaction is not detectable experimentally--or by the neutralisation of Bcl-2-like proteins. Here we discuss the context in which these models are placed and attempt to weigh the evidence.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism
  • Cytochromes c / metabolism*
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Models, Biological*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-2-Associated X Protein / metabolism*


  • Apoptosis Regulatory Proteins
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cytochromes c