Apoptosis-inducing factor (AIF): Key to the conserved caspase-independent pathways of cell death?

Céline Candé, Francesco Cecconi, Philippe Dessen, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous pro-apoptotic signal transducing molecules act on mitochondria and provoke the permeabilization of the outer mitochondrial membrane, thereby triggering the release of potentially toxic mitochondrial proteins. One of these proteins, apoptosis-inducing factor (AIF), is a phylogenetically old flavoprotein which, in healthy cells, is confined to the mitochondrial intermembrane space. Upon lethal signaling, AIF translocates, via the cytosol, to the nucleus where it binds to DNA and provokes caspase-independent chromatin condensation. The crystal structures of both human and mouse AIF have been determined, and the fine mechanisms accounting for its oxidoreductase activity and its electrostatic interaction with double-stranded DNA have been elucidated. Importantly, the apoptogenic and oxidoreductase functions of AIF can be dissociated. Thus, mutations that abolish the AIF-DNA interaction suppress AIF-induced chromatin condensation, yet have no effect on the NADH oxidase activity. Recent studies suggest AIF to be a major factor determining caspase-independent neuronal death, emphasizing the central role of mitochondria in the control of physiological and pathological cell demise.

Original languageEnglish
Pages (from-to)4727-4734
Number of pages8
JournalJournal of Cell Science
Volume115
Issue number24
DOIs
Publication statusPublished - Dec 15 2002

Keywords

  • Apoptosis
  • Caspases
  • Cell death

ASJC Scopus subject areas

  • Cell Biology

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