Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death

M. Thomenius, C. D. Freel, S. Horn, R. Krieser, E. Abdelwahid, R. Cannon, S. Balasundaram, K. White, S. Kornbluth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die.

Original languageEnglish (US)
Pages (from-to)1640-1650
Number of pages11
JournalCell Death and Differentiation
Volume18
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Drosophila
  • apoptosis
  • dMFN
  • mitochondria
  • mitofusins
  • reaper

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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