Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis.
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.
Tanaka
Toru
T
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hosoi
Fumihito
F
Yamaguchi-Iwai
Yuko
Y
Nakamura
Hajime
H
Masutani
Hiroshi
H
Ueda
Shugo
S
Nishiyama
Akira
A
Takeda
Shunichi
S
Wada
Hiromi
H
Spyrou
Giannis
G
Yodoi
Junji
J
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002645:Chickens; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D013879:Thioredoxins