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JCS ePress
online publication date 17 Aug 2004
doi: 10.1242/jcs.01356
Research Article
Regulation of cytoplasmic stress granules by apoptosis-inducing factor
Céline Candé,
Nicola Vahsen,
Didier Métivier,
Hélène Tourrière,
Karim Chebli,
Carmen Garrido,
Jamal Tazi,
and
Guido Kroemer*
* Author for correspondence (e-mail: kroemer{at}igr.fr)
Stress granules (SG) are dynamic cytoplasmic foci in which stalled translation initiation complexes accumulate. In conditions of acute cellular redox, stress cells manipulated to lose the expression of apoptosis-inducing factor (AIF) nucleate SG signature proteins (e.g. TIA-1, PABP1) more efficiently than AIF-positive controls. AIF also inhibited SG formation induced by the RasGAP-associated endoribonuclease G3BP. Retransfection of mouse AIF into cells subjected to human AIF-specific siRNA revealed that only AIF imported into mitochondria could repress SGs and that redox-active domains of AIF, which are dispensable for its apoptogenic action, were required for SG inhibition. In response to oxidative stress, AIF-negative cells were found to deplete non-oxidized glutathione more rapidly than AIF-expressing cells. Exogenous supplementation of glutathione inhibited SG formation elicited by arsenate or G3BP. Together, these data suggest that the oxidoreductase function of AIF is required for the maintenance of glutathione levels in stress conditions and that glutathione is a major regulator of SG.
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© The Company of Biologists Ltd 2004