Table 1.
Major roles of NRF2 in ferroptosis (via regulating downstream genes).
| Symbol | Whole Name | Function | Upregulation or Downregulation | Main Factors for Inhibiting Ferroptosis |
|---|---|---|---|---|
| ABCB6 | ATP-binding cassette subfamily B member 6 | Heme synthesis (transport protoporphyrin to mitochondria) |
↑upregulation | Decrease the capacity of LIP |
| FECH | Ferrochelatase | Heme synthesis (insert ferrous iron into protoporphyrin) |
↑upregulation | Decrease the capacity of LIP |
| FTH1 | Ferritin heavy chain 1 | Iron storage (oxidize ferrous iron into ferric iron) |
↓downregulation | Decrease the capacity of LIP |
| FTL | Ferritin light chain | Iron storage (stabilize ferritin) |
↓downregulation | Decrease the capacity of LIP |
| FPN1 | Ferroportin 1 | Iron excretion | ↑upregulation | Decrease the capacity of LIP |
| HO-1 | Heme-oxygenase 1 | Heme degradation (decompose heme into ferrous iron and biliverdin) |
↑upregulation | Increase the capacity of LIP but generate antioxidants (HO-1 exerts dual effects on ferroptosis) |
| BLVRA/B | Biliverdin reductase A/B | Heme degradation (metabolize biliverdin into bilirubin) |
↑upregulation | Generate antioxidant: bilirubin |
| HERC2 | HECT and RLD domain containing E3 ubiquitin protein ligase 2 | Inhibit ferritinophagy (NCOA4 and FBXL5 ubiquitination and degradation) | ↑upregulation | Decrease the capacity of LIP |
| SLC7A11 | Solute carrier family 7 member 11 | GSH synthesis (import cystine and export glutamate) |
↑upregulation | Generate antioxidant: GSH |
| SLC1A5 | Solute carrier family 1 member 5 | GSH synthesis (absorb glutamine) |
↑upregulation | Generate antioxidant: GSH |
| TXN/TXNRD1 | Thioredoxin/Thioredoxin reductase 1 | GSH synthesis (reduce cystine to cysteine) |
↑upregulation | Generate antioxidant: GSH |
| GCLC/GCLM | Glutamate-cysteine ligase catalytic/modifier subunits | GSH synthesis (connect glutamate and cysteine) |
↑upregulation | Generate antioxidant: GSH |
| GSS | Glutathione synthetase | GSH synthesis (connect glycine and γ-glutamyl cysteine) |
↑upregulation | Generate antioxidant: GSH |
| GSR | Glutathione-disulfide reductase | GSH synthesis (reduce GSSG to GSH) |
↑upregulation | Generate antioxidant: GSH |
| GPX4 | Glutathione peroxidase 4 | ROS detoxification (reduce lipid peroxides by oxidizing GSH to GSSG) |
↑upregulation | Decrease the accumulation of lipid peroxides |
| FSP1 | Ferroptosis-suppressor-protein 1 | Ubiquinol synthesis (convert ubiquinone to ubiquinol with NAD(P)H) |
↑upregulation | Generate antioxidant: ubiquinol |
| PPARγ | Peroxisome proliferator-activated receptor gamma | ROS detoxification (mitigate lipid peroxidation as a nuclear receptor) |
↑upregulation | Decrease the accumulation of lipid peroxides |
| NR0B2 | Nuclear receptor subfamily 0, group B, member 2 | ROS detoxification (mitigate lipid peroxidation as a nuclear receptor) |
↑upregulation | Decrease the accumulation of lipid peroxides |