The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling.
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.
Mancini
M
M
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nicholson
D W
DW
Roy
S
S
Thornberry
N A
NA
Peterson
E P
EP
Casciola-Rosen
L A
LA
Rosen
A
A
D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D007938:Leukemia; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D011498:Protein Precursors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases