The transcription factor (nuclear factor-erythroid 2 p45-related factor 2, NRF2) is a master regulator of the cellular response to oxidative insults. While antioxidant response enzymes are well-characterized transcriptional targets of NRF2, it is recently becoming clear that NRF2 also supports cellular detoxification through metabolic rewiring to support the antioxidant systems.

In this chapter, we discuss the regulation of NRF2 and how NRF2 activation promotes the antioxidant defense of cells. Furthermore, we discuss how reactive oxygen species influence cellular metabolism and how this affects antioxidant function. We also discuss how NRF2 reprograms cellular metabolism to support the antioxidant response and how this functions to funnel metabolic intermediates into antioxidant pathways. This chapter concludes by exploring how these factors may contribute to both normal physiology and disease.