Details

Autor(en) / Beteiligte

• Kim, Stephanie
• Ge, Jianning
• Kim, Dokyun
• Lee, Jae Jin
• Choi, Youn Jung
• Chen, Weiqiang
• Bowman, James W
• Foo, Suan-Sin
• Chang, Lin-Chun
• Liang, Qiming
• Hara, Daiki
• Choi, Inpyo
• Kim, Myung Hee
• Eoh, Hyungjin
• Jung, Jae U

Titel

TXNIP-mediated crosstalk between oxidative stress and glucose metabolism

Ist Teil von

• PloS one, 2024-02, Vol.19 (2), p.e0292655-e0292655

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.