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. 2021 Sep 22;47:102139. doi: 10.1016/j.redox.2021.102139

Fig. 9.

Fig. 9

Water-tank analogy and reduced KEAP1-NRF2 mathematical model. Schematic illustrations of the water-tank analogy for KEAP1-dependent NRF2 degradation, sequestration, and nuclear translocation for (A) class I–V and (B) class VI activators. Large tank: cytosol, Small tank: nucleus, Height of the interface wall between large and small tanks: abundance of available cytosolic KEAP1 (note in B the height is lowered as class VI activator level increases to titrate more KEAP1 away), Water: NRF2, Tap: NRF2 production, Drain: KEAP1-dependent NRF2 degradation, Stopper: class I–V or class VI NRF2 activator. To reduce clutter for clarity, KEAP1-independent NRF2 degradation and nuclear NRF2 degradation are not shown. (C) Reduced KEAP1-NRF2 mathematical model for NRF2 activation by class I–V and class VI activators. (D) Predicted differential free nuclear NRF2 dose-response for class I–V and class VI activators.