Pre-processed caspase-9 contained in mitochondria participates in apoptosis

Cell Death Differ. 2002 Jan;9(1):82-8. doi: 10.1038/sj.cdd.4400932.


As shown here, mitochondria purified from different organs (liver, brain, kidney, spleen and heart) contain both pro-caspase-9 and the processed, mature form of caspase-9. Purified liver mitochondria release mature caspase-9 upon induction of permeability transition in vitro. This is accompanied by a discrete increase in the enzymatic cleavage of pro-caspase-9 substrates. We found that SHEP neuroblastoma cells constitutively contain pre-processed caspase-9 in their mitochondria, using a combination of subcellular fractionation and immunofluorescence with an antibody specific for the processed caspase. This is a cell type-specific phenomenon since HeLa cells mitochondria mainly contain pro-caspase-9 and comparatively little processed caspase-9. Upon introduction of apoptosis, mitochondrial pro-caspase-9 translocates to the cytosol and to the nucleus. This phenomenon is inhibited by transfection with Bcl-2. In synthesis, we report the unexpected finding that mitochondria can contain a pre-processed caspase isoform in non-apoptotic cells. Bcl-2-mediated regulation of mitochondrial membrane permeabilization may contribute to apoptosis control by preventing mitochondrial, pre-processed caspase-9 from interacting with its cytosolic activators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Caspase 9
  • Caspases / metabolism
  • Caspases / physiology*
  • Cell Nucleus / enzymology
  • Cytosol / enzymology
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Mitochondria / enzymology*
  • Neuroblastoma
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology
  • Staurosporine / pharmacology
  • Tumor Cells, Cultured


  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • CASP9 protein, human
  • Caspase 9
  • Caspases
  • Staurosporine