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

doi:10.1073/pnas.0606528103

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

541 Scopus citations

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 language	English (US)
Pages (from-to)	18314-18319
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	103
Issue number	48
DOIs	https://doi.org/10.1073/pnas.0606528103
State	Published - Nov 28 2006

Keywords

Excitotoxicity
Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

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10.1073/pnas.0606528103

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@article{b840c892a2934a0483c765942b183a31,

title = "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.",

keywords = "Excitotoxicity, Poly(ADP-ribose) polymerase",

author = "Yu, {Seong Woon} and Andrabi, {Shaida A.} and Hongmin Wang and No, {Soo Kim} and Poirier, {Guy G.} and Dawson, {Ted M.} and Dawson, {Valina L.}",

year = "2006",

month = nov,

day = "28",

doi = "10.1073/pnas.0606528103",

language = "English (US)",

volume = "103",

pages = "18314--18319",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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publisher = "National Academy of Sciences",

number = "48",

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TY - JOUR

T1 - Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death

AU - Yu, Seong Woon

AU - Andrabi, Shaida A.

AU - Wang, Hongmin

AU - No, Soo Kim

AU - Poirier, Guy G.

AU - Dawson, Ted M.

AU - Dawson, Valina L.

PY - 2006/11/28

Y1 - 2006/11/28

N2 - 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.

AB - 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.

KW - Excitotoxicity

KW - Poly(ADP-ribose) polymerase

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U2 - 10.1073/pnas.0606528103

DO - 10.1073/pnas.0606528103

M3 - Article

C2 - 17116881

AN - SCOPUS:33845317242

SN - 0027-8424

VL - 103

SP - 18314

EP - 18319

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 48

ER -

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

Abstract

Keywords

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