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© The Rockefeller University Press, 0021-9525/2002/3/1089 $5.00
The Journal of Cell Biology, Volume 156, Number 6, March 18, 2002 1089-1098

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

¹ Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide SA 5000, Australia
² Division of Biology, California Institute of Technology, Pasadena, CA 91125

Address correspondence to Sharad Kumar, The Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, P.O. Box 14, Rundle Mall, Adelaide SA 5000, Australia. Tel.: 61-88-222-3738. Fax: 61-88-222-3139. E-mail: sharad.kumar{at}imvs.sa.gov.au

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.

Key Words: DRONC; caspase activation; DRICE; apoptosis; apoptosome

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