Schematic representation of the mechanism of action of MitoQ during colitis. Increased generation of mtROS in the damaged epithelium and activated macrophages leads to dissociation of TXNIP from the TXNIP-TRX complex. Dissociated TXNIP binds to NLRP3 protein and activates the NLRP3 inflammasome complex, which is responsible for cleavage of pro-inflammatory cytokines pro-IL-1 beta and pro-IL-18 into their active forms, thereby increasing intestinal permeability and tissue injury. Moreover, the NLRP3 inflammasome complex activates the adaptive immune system and exacerbates inflammation. Suppressing mtROS with MitoQ can suppress this pathway and inhibit cytokines release, thereby ameliorating inflammation during colitis.
Dashdorj et al. BMC Medicine 2013 11:178 doi:10.1186/1741-7015-11-178