Altered cytochrome c display precedes apoptotic cell death in Drosophila

Johnson Varkey, Po Chen, Ronald Jemmerson, John M. Abrams

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)701-710
Number of pages10
JournalJournal of Cell Biology
Volume144
Issue number4
DOIs
StatePublished - Feb 22 1999

Keywords

  • Apoptosis
  • Cytochrome c
  • Drosophila
  • Programmed cell death

ASJC Scopus subject areas

  • Cell Biology

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