Physiological and Pathophysiological Roles of Thioredoxin Interacting Protein: A Perspective on Redox Inflammation and Metabolism

Significance: Thioredoxin interacting protein (TXNIP) is a member of the arrestin fold superfamily with important cellular functions, including cellular transport, mitochondrial energy generation, and protein cycling. It is the only arrestin-domain protein known to covalently bind to thioredoxin and plays roles in glucose metabolism, inflammation, apoptosis, and cancer. Recent Advances: The crystal structure of the TXNIP-thioredoxin complex provided details about this fascinating interaction. Recent studies showed that TXNIP is induced by endoplasmic reticulum (ER) stress, activates NLR family pyrin domain containing 3 (NLRP3) inflammasomes, and can regulate glucose transport into cells. The tumor suppressor role of TXNIP in various cancer types and the role of TXNIP in fructose absorption are now described. Critical Issues: The influence of TXNIP on redox state is more complex than its interaction with thioredoxin. Future Directions: It is incompletely understood which functions of TXNIP are thioredoxin-dependent. It is also unclear whether TXNIP binding can inhibit glucose transporters without endocytosis. TXNIP-regulated control of ER stress should also be investigated further. Antioxid. Redox Signal. 38, 442–460.