Regulation of cytoplasmic stress granules by apoptosis-inducing factor
Regulation of cytoplasmic stress granules by apoptosis-inducing factor
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DOI：
10.1242/jcs.01356
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发表时间：
2004-09-01
影响因子：
4
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Candé, C;Vahsen, N;Kroemer, G
应激颗粒（SG）是细胞质内聚集的一种动态的翻译起始复合物。在急性细胞氧化还原的条件下，被操纵以失去凋亡诱导因子（AIF）表达的应激细胞比AIF阳性对照更有效地使SG特征蛋白（例如TIA-1、PABP 1）成核。AIF还抑制由RasGAP相关的核糖核酸内切酶G3 BP诱导的SG形成。将小鼠AIF再转染到经受人AIF特异性siRNA的细胞中揭示，只有导入线粒体的AIF才能抑制SG，并且AIF的氧化还原活性结构域（其具有促凋亡作用）是SG抑制所需的。在对氧化应激的反应中，发现AIF阴性细胞比AIF表达细胞更快地消耗非氧化型谷胱甘肽。外源性补充谷胱甘肽可抑制由砷酸盐或G3 BP引起的SG形成。总之，这些数据表明，AIF的氧化还原酶功能是维持应激条件下谷胱甘肽水平所必需的，谷胱甘肽是SG的主要调节剂。
Stress granules (SG) are dynamic cytoplasmic foci in which stalled translation initiation complexes accumulate. In conditions of acute cellular redox, stress cells manipulated to lose the expression of apoptosis-inducing factor (AIF) nucleate SG signature proteins (e.g. TIA-1, PABP1) more efficiently than AIF-positive controls. AIF also inhibited SG formation induced by the RasGAP-associated endoribonuclease G3BP. Retransfection of mouse AIF into cells subjected to human AIF-specific siRNA revealed that only AIF imported into mitochondria could repress SGs and that redox-active domains of AIF, which are dispensable for its apoptogenic action, were required for SG inhibition. In response to oxidative stress, AIF-negative cells were found to deplete non-oxidized glutathione more rapidly than AIF-expressing cells. Exogenous supplementation of glutathione inhibited SG formation elicited by arsenate or G3BP Together, these data suggest that the oxidoreductase function of AIF is required for the maintenance of glutathione levels in stress conditions and that glutathione is a major regulator of SG.