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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.
FlyBase ID
FBrf0205458
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC2907157 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    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 (1)
    Alleles (16)
    Genes (14)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (4)
    Transgenic Constructs (10)