Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.
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.
Type
Journal articleSubject
AnimalsApoptosis
Cell Line
Drosophila Proteins
Drosophila melanogaster
Gamma Rays
HeLa Cells
Humans
Membrane Proteins
Mitochondria
Neuropeptides
Protein Binding
Permalink
https://hdl.handle.net/10161/8381Published Version (Please cite this version)
10.1038/cdd.2011.26Publication Info
Thomenius, M; Freel, CD; Horn, S; Krieser, R; Abdelwahid, E; Cannon, R; ... Kornbluth,
S (2011). Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell
death. Cell Death Differ, 18(10). pp. 1640-1650. 10.1038/cdd.2011.26. Retrieved from https://hdl.handle.net/10161/8381.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Sally A. Kornbluth
Jo Rae Wright University Professor
Our lab studies the regulation of complex cellular processes, including cell cycle
progression and programmed cell death (apoptosis). These tightly orchestrated processes
are critical for appropriate cell proliferation and cell death, and when they go awry
can result in cancer and degenerative disorders. Within these larger fields, we have
focused on understanding the cellular mechanisms that prevent the onset of mitosis
prior to the completion of DNA replication, the process

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles