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

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.

SUBMITTER: Yu SW

PROVIDER: S-EPMC1838748 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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

Yu Seong-Woon SW Andrabi Shaida A SA Wang Hongmin H Kim No Soo NS Poirier Guy G GG Dawson Ted M TM Dawson Valina L VL

Proceedings of the National Academy of Sciences of the United States of America 20061120 48

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 ...[more]

PMID: 17116881

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