Mediation of poty(ADP-ribose) polymerase-1 - Dependent cell death by apoptosis-inducing factor

Seong Woon Yu, Hongmin Wang, Marc F. Poitras, Carmen Coombs, William J. Bowers, Howard J. Federoff, Guy G. Poirier, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalArticlepeer-review

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. N-methyl-N′-nitro-N-nitrosoguanidine, H2O2, and N-methyl-D-aspartate induce AIF translocation and cell death, which is prevented by PARP inhibitors or genetic knockout of PARP-1, but is caspase independent. Microinjection of an antibody to AIF protects against PARP-1-dependent cytotoxicity. These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalScience
Volume297
Issue number5579
DOIs
StatePublished - Jul 12 2002

ASJC Scopus subject areas

  • General

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