Caspase-2-induced apoptosis requires bid cleavage: a physiological role for bid in heat shock-induced death

Mol Biol Cell. 2006 May;17(5):2150-7. doi: 10.1091/mbc.e05-12-1107. Epub 2006 Feb 22.


The mechanisms through which Caspase-2 leads to cell death are controversial. Here we show, using a combination of cell-free and cell culture-based approaches, that cleavage of the Bcl-2-family protein Bid is required for the induction of apoptosis by Caspase-2. Caspase-2 promoted cytochrome c release from mitochondria in the presence of cytosol from wild-type, but not Bid-deficient, mouse embryonic fibroblasts (MEFs). Recombinant wild-type Bid, but not a noncleavable mutant (D59E), restored cytochrome c release. Similarly, Bid-null MEFs were relatively resistant to apoptosis triggered by active Caspase-2, and apoptosis was restored in Bid-null cells by the expression of wild-type, but not D59E, Bid. Finally, Bid-null MEFs were substantially more resistant to apoptosis induced by heat shock, which has been shown to be dependent on apical activation of Caspase-2. The data are consistent with a model in which Caspase-2 induces apoptosis via cleavage of Bid at D59 and the subsequent engagement of the mitochondrial (intrinsic) pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein / genetics
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Caspase 2
  • Caspases / metabolism*
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Cytosol / metabolism
  • Embryo, Mammalian / cytology
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Hot Temperature*
  • Mice
  • Mitochondria / metabolism
  • Mutation


  • BH3 Interacting Domain Death Agonist Protein
  • Bid protein, mouse
  • Cytochromes c
  • Caspase 2
  • Caspases