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

Marie Mancini, Donald W. Nicholson, Sophie Roy, Nancy A. Thornberry, Erin P. Peterson, Livia A. Casciola-Rosen, Antony Rosen

Research output: Contribution to journalArticlepeer-review

365 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1485-1495
Number of pages11
JournalJournal of Cell Biology
Volume140
Issue number6
DOIs
StatePublished - Mar 23 1998

ASJC Scopus subject areas

  • Cell Biology

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