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© The Rockefeller University Press, 0021-9525/1999//701 $5.00
The Journal of Cell Biology, Volume 144, Number 4, , 1999 701-710

Altered Cytochrome c Display Precedes Apoptotic Cell Death in Drosophila

Johnson Varkey^*, Po Chen^*, Ronald Jemmerson, and John M. Abrams^*

^* Department of Cell Biology and Neuroscience, University of Texas, Southwestern Medical Center, Dallas, Texas 75235-9039; and Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Drosophila affords a genetically well-defined system to study apoptosis in vivo. It offers a powerful extension to in vitro models that have implicated a requirement for cytochrome c in caspase activation and apoptosis. We found that an overt alteration in cytochrome c anticipates programmed cell death (PCD) in Drosophila tissues, occurring at a time that considerably precedes other known indicators of apoptosis. The altered configuration is manifested by display of an otherwise hidden epitope and occurs without release of the protein into the cytosol. Conditional expression of the Drosophila death activators, reaper or grim, provoked apoptogenic cytochrome c display and, surprisingly, caspase activity was necessary and sufficient to induce this alteration. In cell-free studies, cytosolic caspase activation was triggered by mitochondria from apoptotic cells but identical preparations from healthy cells were inactive. Our observations provide compelling validation of an early role for altered cytochrome c in PCD and suggest propagation of apoptotic physiology through reciprocal, feed-forward amplification involving cytochrome c and caspases.

Key Words: apoptosis • programmed cell death • cytochrome c • Drosophila

Abbreviations used in this paper: PARP, poly ADP-ribose polymerase; rpr, reaper; SL2, Schneider L2 cells.

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