Splitting the apoptosome

Cell Cycle. 2004 Apr;3(4):446-8. Epub 2004 Apr 1.

Abstract

Assembly of the apoptosome in response to mitochondrial permeabilization, the hallmark of the intrinsic apoptotic pathway, involves binding of cytochrome c to Apaf1, recruitment and auto-processing of the apical/signaling pro-caspase-9, and coupled activation of downstream/executioner caspases like caspase 3. Evidence now indicates that certain apoptotic cascades can bypass the apoptosome and activate caspase-9 independent of the mitochondria. Recently, we have demonstrated that caspase-9 can be activated in Apaf1-mutant primary myoblasts, but not fibroblasts, in response to stimuli that are known to act via the mitochondria. Thus, apoptosomal activation of caspase-9 seems to represent only one of the routes for its activation; other pathways, some of which are yet to be discovered, can bypass the requirement for Apaf1 and activate caspase-9 in a tissue and context specific manner.

MeSH terms

  • Animals
  • Apoptosis*
  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans
  • Caspase 3
  • Caspase 9
  • Caspases / metabolism
  • Endoplasmic Reticulum / metabolism
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Mitochondria / metabolism*
  • Models, Biological
  • Mutation
  • Protein Structure, Tertiary
  • Proteins / metabolism

Substances

  • APAF1 protein, human
  • Apaf1 protein, mouse
  • Apoptotic Protease-Activating Factor 1
  • Proteins
  • CASP3 protein, human
  • CASP9 protein, human
  • Casp3 protein, mouse
  • Casp9 protein, mouse
  • Caspase 3
  • Caspase 9
  • Caspases