Reference Report

Reference
Citation	Joza, N., Galindo, K., Pospisilik, J.A., Benit, P., Rangachari, M., Kanitz, E.E., Nakashima, Y., Neely, G.G., Rustin, P., Abrams, J.M., Kroemer, G., Penninger, J.M. (2008). The molecular archaeology of a mitochondrial death effector: AIF in Drosophila. Cell Death Differ. 15(6): 1009--1018. (Export to RIS)
FlyBase ID	FBrf0205458
Publication Type	Research paper
PubMed ID	18309327
PubMed Abstract	Apoptosis-inducing factor (AIF) is a phylogenetically conserved redox-active flavoprotein that contributes to cell death and oxidative phosphorylation in Saccharomyces cerevisiae, Caenorhabditis elegans, mouse and humans. AIF has been characterized as a caspase-independent death effector that is activated by its translocation from mitochondria to the cytosol and nucleus. Here, we report the molecular characterization of AIF in Drosophila melanogaster, a species in which most cell deaths occur in a caspase-dependent manner. Interestingly, knockout of zygotic D. melanogaster AIF (DmAIF) expression using gene targeting resulted in decreased embryonic cell death and the persistence of differentiated neuronal cells at late embryonic stages. Although knockout embryos hatch, they undergo growth arrest at early larval stages, accompanied by mitochondrial respiratory dysfunction. Transgenic expression of DmAIF misdirected to the extramitochondrial compartment (DeltaN-DmAIF), but not wild-type DmAIF, triggered ectopic caspase activation and cell death. DeltaN-DmAIF-induced death was not blocked by removal of caspase activator Dark or transgenic expression of baculoviral caspase inhibitor p35, but was partially inhibited by Diap1 overexpression. Knockdown studies revealed that DeltaN-DmAIF interacts genetically with the redox protein thioredoxin-2. In conclusion, we show that Drosophila AIF is a mitochondrial effector of cell death that plays roles in developmentally regulated cell death and normal mitochondrial function.
DOI	10.1038/cdd.2008.24
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Cell Death Differ.
Title	Cell Death and Differentiation
Publication Year	1994-
ISBN/ISSN	1350-9047
Data from Reference
Aberrations (2)
	Df(3L)H99 Dp(2;2)AIF^T52
Alleles (19)
	AIF^Scer\SceI.RS AIF^{Scer\UAS.T:Hsap\MYC} AIF^T52.3' AIF^T52.5' AIF^{ΔN.Scer\UAS.T:Hsap\MYC} Ark^CD4 Avic\GFP^{S65T.Scer\UAS.T:Ivir\HA1,T:Hsap\mito} BacA\p35^Scer\UAS.cHa Dredd^B118 Iap2^Scer\UAS.cMa p53^-ns.3' p53^-ns.5' Scer\GAL4^da.G32 Scer\GAL4^ey.PH Scer\GAL4^pnr-MD237 th^Scer\UAS.cMb Trx-2^GD10505 w^+mC w^+mW.hs
Constructs (10)
	P{FRT(w^hs.AIF^Scer\SceI.RS)} P{GAL4-da.G32} P{GAL4-ey.H} P{GD10505} P{UAS-AIF.myc} P{UAS-AIF.ΔN.myc} P{UAS-Iap2.M} P{UAS-mito-HA-GFP.AP} P{UAS-p35.H} P{UAS-th.Mb}
Genes (15)
	AIF Ark Avic\GFP BacA\p35 Dredd exex Gpdh Iap2 Kr p53 Scer\GAL4 T:Hsap\MYC th Trx-2 w
Insertions (1)
	P{GawB}pnr^MD237
Natural transposons (1)
	P-element