Figure 3.

Schematic of Nrf2 response to mitochondrial hydrogen peroxide production. Hydrogen peroxide (H₂O₂)-based molecular signal transduction involving the constitutive Nrf2 transcription factor, which is normally targeted for ubiquitination and degradation (step 1). Various oxidative and electrophilic stresses can stabilize Nrf2 by the oxidation of the kelch-like ECH-associating protein-1 (Keap1) adaptor molecule, allowing free Nrf2 to translocate to the nucleus. The diagram indicates the role of oxidative damage and increased mitochondrial H₂O₂ production (step 2) in the stabilization of Nrf2 (step 3), and activation of genes that contain the antioxidant response element (ARE) consensus sequence - in this case, superoxide dismutase (SOD2) (step 4).