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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Thomenius, M; Freel, CD; Horn, S; Krieser, R; Abdelwahid, E; Cannon, R; Balasundaram, S; White, K; Kornbluth, S

Published Date

  • October 2011

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 1640 - 1650

PubMed ID

  • 21475305

Pubmed Central ID

  • 21475305

Electronic International Standard Serial Number (EISSN)

  • 1476-5403

International Standard Serial Number (ISSN)

  • 1350-9047

Digital Object Identifier (DOI)

  • 10.1038/cdd.2011.26

Language

  • eng