Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
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DOI：
10.1073/pnas.0606528103
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发表时间：
2006-11-28
影响因子：
11.1
通讯作者：
Dawson, Valina L.
中科院分区：
文献类型：
--
作者：
Yu, Seong-Woon;Andrabi, Shaida A.;Dawson, Valina L.
凋亡诱导因子（AIF）是一种线粒体氧化还原酶，在多聚腺苷二磷酸核糖（PAR）聚合酶-1（PARP-1）激活后释放到细胞质中诱导细胞死亡。PARP-1激活如何导致AIF释放尚不清楚。在这里，我们确定PAR聚合物作为诱导AIF释放的细胞死亡信号。PAR多聚体诱导线粒体AIF释放并易位至细胞核。降解PAR聚合物的PAR糖水解酶阻止PAR P-1依赖性AIF释放。AIF水平降低的细胞对PARP-1依赖性细胞死亡和PAR聚合物细胞毒性具有抗性。这些结果揭示PAR聚合物作为AIF释放因子在PARP-1依赖性细胞死亡中起重要作用。
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 PAR P-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.