2011
DOI: 10.1126/scisignal.2000902
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Abstract: The mitochondrial protein apoptosis-inducing factor (AIF) plays a pivotal role in poly(ADP-ribose) polymerase-1 (PARP-1)-mediated cell death (parthanatos), during which it is released from the mitochondria and translocates to the nucleus. Here, we show that AIF is a high affinity poly(ADP-ribose) (PAR)–binding protein and that PAR binding to AIF is required for parthanatos both in vitro and in vivo. AIF bound PAR at a site distinct from AIF’s DNA binding site and this interaction triggered AIF release from the… Show more

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Cited by 352 publications
(318 citation statements)
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References 42 publications
(74 reference statements)
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“…One candidate mechanism is through interaction with AIF itself. Small population of AIF are located on the cytosolic side of the mitochondrial outer membrane (Yu et al, 2009) and AIF has a putative PAR binding sequence and binding of PAR to AIF seems critical for PARP-1-dependent cell death (Wang et al, 2011). Recently, Iduna was reported to protect the brain from cell death by interfering with PAR polymer-induced cell death .…”
Section: Discussionmentioning
confidence: 99%
“…One candidate mechanism is through interaction with AIF itself. Small population of AIF are located on the cytosolic side of the mitochondrial outer membrane (Yu et al, 2009) and AIF has a putative PAR binding sequence and binding of PAR to AIF seems critical for PARP-1-dependent cell death (Wang et al, 2011). Recently, Iduna was reported to protect the brain from cell death by interfering with PAR polymer-induced cell death .…”
Section: Discussionmentioning
confidence: 99%
“…Cette voie de nécrose dépendante de PARP-1 a également été démontrée comme dépendante des kinases RIP1 et RIP3, soulevant la question d'une nécroptose intrinsèque, en opposition à la nécroptose extrinsèque induite par les récepteurs de mort. Certains travaux ont montré l'importance de la liaison des polymères de PAR pour la libération d'AIF sans activation des calpaïnes, se plaçant dans un type de mort baptisé parthanatos [17]. L'importance de la nécroptose a pu être démontrée dans de nombreuses conditions physiopathologiques, telles que l'inflammation de l'intestin, la perte de la libération de nombreuses cytokines et de médiateurs de l'inflammation : IL8, IL10, TNFα et HMGB1.…”
Section: Mourir Brutalement : Nécrose Régulée Et Necroptosisunclassified
“…[137][138][139] Of note, AIF has recently been shown to possess a high-affinity PAR-binding site, and the physical interaction between PAR and AIF appears to be required for parthanatos, both in vitro and in vivo. 140 Parthanatos have a role in multiple experimental and physiopathological scenarios, including stroke, diabetes, inflammation and neurodegeneration. 141 In line with the original definition of parthanatos, cell death instances should be considered as parthanatic when they depend on early PARP1 activation (i.e., they can be blocked by its chemical and/or genetic inhibition), 142 and exhibit NAD þ plus ATP depletion paralleled by AIF-mediated chromatinolysis.…”
Section: Tentative Definition Of Other Cell Death Modalitiesmentioning
confidence: 99%