Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis
Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis
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DOI：
10.1093/emboj/21.7.1695
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发表时间：
2002-04-02
期刊：
影响因子：
11.4
通讯作者：
Yodoi, J
中科院分区：
文献类型：
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作者：
Tanaka, T;Hosoi, F;Yodoi, J
硫氧还蛋白-2（Trx-2）是硫氧还蛋白超家族的一个成员。线粒体在细胞凋亡的信号转导中起着至关重要的作用。为了研究Trx-2的生物学意义，我们克隆了鸡TRX-2 cDNA，并使用鸡B细胞系DT 40产生条件性Trx-2缺陷细胞的克隆。在这里，我们表明，TRX-2是一个必不可少的基因和TRX-2-缺陷的细胞进行细胞凋亡后，抑制TRX-2转基因，显示细胞内活性氧（ROS）的积累。细胞色素c从线粒体释放，而半胱天冬酶-9和半胱天冬酶-3，但不是半胱天冬酶-8，在抑制TRX-2转基因时被激活。此外，Trx-2和细胞色素c在体外测定中发生免疫共沉淀。这些结果表明，线粒体Trx-2是细胞生存所必需的，在清除线粒体中的ROS和调节线粒体凋亡信号通路中起着至关重要的作用。
Thioredoxin-2 (Trx-2) is a mitochondria-specific member of the thioredoxin superfamily. Mitochondria have a crucial role in the signal transduction for apoptosis. To investigate the biological significance of Trx-2, we cloned chicken TRX-2 cDNA and generated clones of the conditional Trx-2-deficient cells using chicken B-cell line, DT40. Here we show that TRX-2 is an essential gene and that Trx-2-deficient cells undergo apoptosis upon repression of the TRX-2 transgene, showing an accumulation of intracellular reactive oxygen species (ROS). Cytochrome c is released from mitochondria, while caspase-9 and caspase-3, but not caspase-8, are activated upon inhibition of the TRX-2 transgene. In addition, Trx-2 and cytochrome c are co-immunoprecipitated in an in vitro assay. These results suggest that mitochondrial Trx-2 is essential for cell viability, playing a crucial role in the scavenging ROS in mitochondria and regulating the mitochondrial apoptosis signaling pathway.