Mechanisms of cytochrome c release by proapoptotic BCL-2 family members

Biochem Biophys Res Commun. 2003 May 9;304(3):437-44. doi: 10.1016/s0006-291x(03)00615-6.


A crucial amplificatory event in several apoptotic cascades is the nearly complete release of cytochrome c from mitochondria. Proteins of the BCL-2 family which include both anti- and proapoptotic members control this step. Here, we review the proposed mechanisms by which proapoptotic BCL-2 family members induce cytochrome c release. Data support a model in which the apoptotic pathway bifurcates following activation of a "BH3 only" family member. BH3 only molecules induce the activation of the multidomain proapoptotics BAX and BAK, resulting in the permeabilization of the outer mitochondrial membrane and the efflux of cytochrome c. This is coordinated with the activation of a distinct pathway characterized by profound changes of the inner mitochondrial membrane morphology and organization. This mitochondrial remodelling insures complete release of cytochrome c and the onset of mitochondrial dysfunction that is a typical feature of many apoptotic deaths.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Cytochrome c Group / metabolism*
  • Intracellular Membranes / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Mitochondria / metabolism
  • Models, Biological
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Signal Transduction
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein


  • Cytochrome c Group
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein