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  • The EMBO Journal (2002) 21, 1695 - 1703
  • doi:10.1093/emboj/21.7.1695

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

Toru Tanaka1,2, Fumihito Hosoi1, Yuko Yamaguchi-Iwai3, Hajime Nakamura1, Hiroshi Masutani1,4, Shugo Ueda1, Akira Nishiyama1, Shunichi Takeda5, Hiromi Wada2, Giannis Spyrou6 and Junji Yodoi1,4

  1. Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
  2. Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
  3. Department of Applied Molecular Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8315, Japan
  4. Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka 563-8577, Japan
  5. Department of Experimental Radiology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
  6. Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden

Correspondence to:

Junji Yodoi, E-mail: yodoi@virus.kyoto-u.ac.jp

Received 17 August 2001; Accepted 11 February 2002; Revised 11 February 2002

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.

  • Keywords:

    • apoptosis,
    • cytochrome,
    • mitochondria,
    • redox,
    • thioredoxin-2