The role of cytochrome c in caspase activation in Drosophila melanogaster cells

Loretta Dorstyn, Stuart Read, Dimitrios Cakouros, Jun R. Huh, Bruce A. Hay, Sharad Kumar

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161 Citations (Scopus)

Abstract

The release of cytochrome c from mitochondria is necessary for the formation of the Apaf-1 apoptosome and subsequent activation of caspase-9 in mammalian cells. However, the role of cytochrome c in caspase activation in Drosophila cells is not well understood. We demonstrate here that cytochrome c remains associated with mitochondria during apoptosis of Drosophila cells and that the initiator caspase DRONC and effector caspase DRICE are activated after various death stimuli without any significant release of cytochrome c in the cytosol. Ectopic expression of the proapoptotic Bcl-2 protein, DEBCL, also fails to show any cytochrome c release from mitochondria. A significant proportion of cellular DRONC and DRICE appears to localize near mitochondria, suggesting that an apoptosome may form in the vicinity of mitochondria in the absence of cytochrome c release. In vitro, DRONC was recruited to a >700-kD complex, similar to the mammalian apoptosome in cell extracts supplemented with cytochrome c and dATP. These results suggest that caspase activation in insects follows a more primitive mechanism that may be the precursor to the caspase activation pathways in mammals.

Original languageEnglish
Pages (from-to)1089-1098
Number of pages10
JournalJournal of Cell Biology
Volume156
Issue number6
DOIs
Publication statusPublished or Issued - 18 Mar 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Apoptosome
  • Caspase activation
  • DRICE
  • DRONC

ASJC Scopus subject areas

  • Cell Biology

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