Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis

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Abstract
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.