FIG. 13.

Redoxosome formation in IL-1 signaling. Redoxosome (redox active endosomes which produce O₂^•−/H₂O₂) formation has been demonstrated for the activation of NOX2 by IL-1 in MCF7 cells (354). After docking of IL-1 to IL-1R1 MyD88 is recruited as effector, and initiates endosome formation. Then, Rac-1 in its GTP-bound conformation together with superoxide dismutase 1 (SOD1) is transferred to the membrane, resulting in the recruitment of the second effector, NOX2 with all its subunits. O₂^•− produced by NOX leaves the endosome via anionic channels (AC) and is dismutated to H₂O₂ by SOD1. This creates an oxidative environment, which promotes docking of IRAK and TRAF6 to the receptor complex finally leading to NF-κB activation. An analogous pathway works in TNF signaling where TRADD and RIP1 are recruited instead of MyD88 and TRAF2 instead of TRAF6.