Fig. 1: Schematic representation of oxidative stress-induced subcellular TXNIP shuttling and the apoptosis pathway.
From: TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target
Under normal conditions, TXNIP is primarily localized in the nucleus. This allows TRX2 in the mitochondria to remain bound to ASK1, inhibiting the activation of ASK1 and promoting cellular survival. In response to oxidative stress, TXNIP shuttles to the mitochondria, where it competes with ASK1 for TRX2 binding, generating a TXNIP/TRX2 complex and leading to ASK1 phosphorylation. p-ASK1 stimulates Cyto c release into the cytosol, which activates Apaf-1. Apaf-1 oligomerizes into an apoptosome complex. Pro-caspase 9 is recruited to the apoptosome and is activated by autocleavage. Activated caspase 9 cleaves pro-caspase 3 and leads to a programmed apoptosis pathway.
