Fig. 8.

Proposed model for the relationship between NRF2-FOCAD-FAK signaling and cysteine deprivation-induced ferroptosis. Lots of components of the ferroptosis cascade, such as GPX4, SLC7A11, and AKR1B1, could be positively regulated by NRF2. In addition, NRF2 negatively regulated the transcription of FOCAD gene that was essential for the activity of FAK, and the suppression of FAK activity reduced the cellular sensitivity to cysteine (Cys) deprivation-induced ferroptosis via affecting the mitochondrial TCA cycle and the activity of Complex I in mitochondrial ETC.