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

dc.contributor.author Thomenius, M
dc.contributor.author Freel, CD
dc.contributor.author Horn, S
dc.contributor.author Krieser, R
dc.contributor.author Abdelwahid, E
dc.contributor.author Cannon, R
dc.contributor.author Balasundaram, S
dc.contributor.author White, K
dc.contributor.author Kornbluth, S
dc.coverage.spatial England
dc.date.accessioned 2014-03-06T15:59:21Z
dc.date.issued 2011-10
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21475305
dc.identifier cdd201126
dc.identifier.uri https://hdl.handle.net/10161/8381
dc.description.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.
dc.language eng
dc.relation.ispartof Cell Death Differ
dc.relation.isversionof 10.1038/cdd.2011.26
dc.subject Animals
dc.subject Apoptosis
dc.subject Cell Line
dc.subject Drosophila Proteins
dc.subject Drosophila melanogaster
dc.subject Gamma Rays
dc.subject HeLa Cells
dc.subject Humans
dc.subject Membrane Proteins
dc.subject Mitochondria
dc.subject Neuropeptides
dc.subject Protein Binding
dc.title Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21475305
pubs.begin-page 1640
pubs.end-page 1650
pubs.issue 10
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group School of Medicine
pubs.organisational-group Staff
pubs.publication-status Published
pubs.volume 18
dc.identifier.eissn 1476-5403


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