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Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18314-9. Epub 2006 Nov 20.

Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death.

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  • 1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads to AIF release is not known. Here we identify PAR polymer as a cell death signal that induces release of AIF. PAR polymer induces mitochondrial AIF release and translocation to the nucleus. PAR glycohydrolase, which degrades PAR polymer, prevents PARP-1-dependent AIF release. Cells with reduced levels of AIF are resistant to PARP-1-dependent cell death and PAR polymer cytotoxicity. These results reveal PAR polymer as an AIF-releasing factor that plays important roles in PARP-1-dependent cell death.

PMID:
17116881
[PubMed - indexed for MEDLINE]
PMCID:
PMC1838748
Free PMC Article
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