Fig. 1.

In the redox neutral cell, dithiol oxidoreductases TRX, GRX, and PRX bind to and inactivate ASK1. However, cell stressors can induce cellular oxidative imbalance, which causes disulphide bonds to form between the cysteine residues of TRX, GRX, or PRX. As a result, TRX, PRX, and GRX dissociate from ASK1. Unbound ASK1 is then activated by auto-phosphorylation and a large multicomponent complex forms, referred to as the ASK1 signalosome. The ASK1 signalosome promotes the sustained activation of the P38 and JNK signalling cascades which have been associated with damaging inflammatory responses, cell death, and fibrosis in multiple tissues