Peroxiredoxin 3 (PRDX3) and PRDX5 in the mitochondrial matrix reduce hydrogen peroxide (H2O2) with thioredoxin to yield oxidized thioredoxin and water (Yamashita et al. 1999, Knoops et al. 1999, Cao et al. 2007, Nagy et al. 2011). Reduced PRDX5 is a monomer (Declercq et al. 2001) and oxidized PRDX5 is a dimer (Evrard et al. 2004) therefore the enzyme may cycle between states.
Thioredoxin-interacting protein (TXNIP) binds NLRP3. Reactive oxygen species (ROS) such as H2O2 increase this interaction, while the ROS inhibitor APDC blocks it (Zhou et al. 2010). This interaction is proposed to activate the NLRP3 inflammasome.
Heme oxygenase (HMOX1), besides its enzymatic activity of the dimeric membrane protein isoform, also occurs as soluble cytosolic protein. It is probably this form that binds to the NACHT domain of NLRP3, suppressing production of epithelial cell-derived cytokines induced by activation of the NLRP3 inflammasome, and protecting airway epithelium in asthma (Lv et al, 2018).
TXNIP interacts with the redox-active domain of thioredoxin (TRX) and is believed to act as an oxidative stress mediator by inhibiting TRX activity or by limiting its bioavailability (Nishiyama et al. 1999, Liyanage et al. 2007).
ROS induce the dissociation of TXNIP from thioredoxin, freeing TXNIP to subsequently bind NLRP3 and bring about activation of the NLRP3 inflammasome (Zhou et al. 2010).