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.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.identifier

http://www.ncbi.nlm.nih.gov/pubmed/21475305

dc.identifier

cdd201126

dc.identifier.eissn

1476-5403

dc.identifier.uri

https://hdl.handle.net/10161/8381

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death..pdf
Size:
894.5 KB
Format:
Adobe Portable Document Format
Description:
Published version