The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling

J Cell Biol. 1998 Mar 23;140(6):1485-95. doi: 10.1083/jcb.140.6.1485.


Caspase-3-mediated proteolysis is a critical element of the apoptotic process. Recent studies have demonstrated a central role for mitochondrial proteins (e.g., Bcl-2 and cytochrome c) in the activation of caspase-3, by a process that involves interaction of several protein molecules. Using antibodies that specifically recognize the precursor form of caspase-3, we demonstrate that the caspase-3 proenzyme has a mitochondrial and cytosolic distribution in nonapoptotic cells. The mitochondrial caspase-3 precursor is contained in the intermembrane space. Delivery of a variety of apoptotic stimuli is accompanied by loss of mitochondrial caspase-3 precursor staining and appearance of caspase-3 proteolytic activity. We propose that the mitochondrial subpopulation of caspase-3 precursor molecules is coupled to a distinct subset of apoptotic signaling pathways that are Bcl-2 sensitive and that are transduced through multiple mitochondrion-specific protein interactions.

Publication types

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

MeSH terms

  • Apoptosis / immunology*
  • Caspase 3
  • Caspases*
  • Cysteine Endopeptidases / analysis
  • Cysteine Endopeptidases / metabolism*
  • Cytosol / enzymology
  • Cytosol / ultrastructure
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / enzymology
  • Keratinocytes / ultrastructure
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / enzymology
  • Killer Cells, Natural / ultrastructure
  • Leukemia
  • Microscopy, Electron
  • Mitochondria / enzymology
  • Mitochondria / ultrastructure
  • Protein Precursors / analysis
  • Protein Precursors / metabolism*
  • Signal Transduction / immunology*
  • Tumor Cells, Cultured


  • Protein Precursors
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases