The molecular archaeology of a mitochondrial death effector

AIF in Drosophila

N. Joza, K. Galindo, J. A. Pospisilik, P. Benit, M. Rangachari, E. E. Kanitz, Y. Nakashima, G. G. Neely, P. Rustin, J. M. Abrams, G. Kroemer, J. M. Penninger

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 (ΔN-DmAIF), but not wild-type DmAIF, triggered ectopic caspase activation and cell death. ΔN-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 ΔN-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.

Original languageEnglish (US)
Pages (from-to)1009-1018
Number of pages10
JournalCell Death and Differentiation
Volume15
Issue number6
DOIs
StatePublished - Jun 2008

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Archaeology
Apoptosis Inducing Factor
Drosophila melanogaster
Drosophila
Cell Death
Caspases
Oxidation-Reduction
Flavoproteins
Thioredoxins
Caspase Inhibitors
Gene Targeting
Oxidative Phosphorylation
Caenorhabditis elegans
Cytosol
Saccharomyces cerevisiae
Mitochondria
Embryonic Structures

ASJC Scopus subject areas

  • Cell Biology

Cite this

Joza, N., Galindo, K., Pospisilik, J. A., Benit, P., Rangachari, M., Kanitz, E. E., ... Penninger, J. M. (2008). The molecular archaeology of a mitochondrial death effector: AIF in Drosophila. Cell Death and Differentiation, 15(6), 1009-1018. https://doi.org/10.1038/cdd.2008.24

The molecular archaeology of a mitochondrial death effector : AIF in Drosophila. / 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.

In: Cell Death and Differentiation, Vol. 15, No. 6, 06.2008, p. 1009-1018.

Research output: Contribution to journalArticle

Joza, N, Galindo, K, Pospisilik, JA, Benit, P, Rangachari, M, Kanitz, EE, Nakashima, Y, Neely, GG, Rustin, P, Abrams, JM, Kroemer, G & Penninger, JM 2008, 'The molecular archaeology of a mitochondrial death effector: AIF in Drosophila', Cell Death and Differentiation, vol. 15, no. 6, pp. 1009-1018. https://doi.org/10.1038/cdd.2008.24
Joza N, Galindo K, Pospisilik JA, Benit P, Rangachari M, Kanitz EE et al. The molecular archaeology of a mitochondrial death effector: AIF in Drosophila. Cell Death and Differentiation. 2008 Jun;15(6):1009-1018. https://doi.org/10.1038/cdd.2008.24
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. / The molecular archaeology of a mitochondrial death effector : AIF in Drosophila. In: Cell Death and Differentiation. 2008 ; Vol. 15, No. 6. pp. 1009-1018.
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