FIG. 1.

Schematic representation showing interaction of sirtuins with NRF2 that regulates the expression of several antioxidant and detoxification genes. Under oxidative stress, the KEAP1-CUL3 ubiquitination system is disrupted, which allows NRF2 to translocate into the nucleus where it forms a heterodimer with one of the Maf proteins and binds to the ARE or ERE in the promoter region of antioxidative stress response genes resulting in mitochondrial biogenesis and antioxidant redox signaling. ARE, antioxidant response element; CUL3, cullin 3; ERE, electrophilic response element; GSH, glutathione; HO-1, heme oxygenase 1; KEAP1, kelch-like ECH-associated protein 1; NRF2, nuclear factor E2-related factor 2; ROS, reactive oxygen species; SOD, superoxide dismutase.