title: Thioredoxin/Txnip: redoxisome, as a redox switch for the pathogenesis of diseases.
abstract: During the past few decades, it has been widely recognized that Reduction-Oxidation (redox) responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin1 (Trx1) and Thioredoxin2 (Trx2), mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/thioredoxin binding protein-2/vitamin D3 upregulated protein) directly binds to Trx1 and Trx2 (Trx) and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP-3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named "Redoxisome," consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes.
authors.affiliation: Institute for Virus Research, Kyoto University , Kyoto , Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshihara
authors.affiliation: Institute for Virus Research, Kyoto University , Kyoto , Japan.
authors.forename: So
authors.initials: S
authors.lastname: Masaki
authors.affiliation: Institute for Virus Research, Kyoto University , Kyoto , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Institute for Virus Research, Kyoto University , Kyoto , Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Advanced Chemical Technology Center in Kyoto (ACT Kyoto), JBPA Research Institute , Kyoto , Japan ; Redox Bio Science Inc. , Kyoto , Japan.
authors.forename: Hai
authors.initials: H
authors.lastname: Tian
authors.affiliation: Institute for Virus Research, Kyoto University , Kyoto , Japan ; Advanced Chemical Technology Center in Kyoto (ACT Kyoto), JBPA Research Institute , Kyoto , Japan ; Redox Bio Science Inc. , Kyoto , Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
keywords: Txnip; diabetes mellitus; inflammation; redox regulation; redoxisome; thioredoxin