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

Seong Woon Yu, Shaida A. Andrabi, Hongmin Wang, Soo Kim No, Guy G. Poirier, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)18314-18319
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number48
DOIs
StatePublished - Nov 28 2006

Keywords

  • Excitotoxicity
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • General

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