Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death.
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.
Yu
Seong-Woon
SW
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Andrabi
Shaida A
SA
Wang
Hongmin
H
Kim
No Soo
NS
Poirier
Guy G
GG
Dawson
Ted M
TM
Dawson
Valina L
VL
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D021381:Protein Transport
D051033:Apoptosis Inducing Factor; D011108:Polymers; D011064:Poly Adenosine Diphosphate Ribose