Table 2.
Ferroptosis-related signaling molecules and signaling pathways
| Signaling molecules | Signaling pathways | Effects of signaling molecules | Mechanisms | References |
|---|---|---|---|---|
| ATF4 | PERK-ATF4-HSPA5 | Inhibition of ferroptosis in glioma cells. | PERK-upregulated ATF4 inducted HSPA5 expression and increased GPX4. | 85, 99. |
| GCN2-eIF2α-ATF4 | Induction of ferroptosis in human triple negative breast cancer cells. | GCN2 activation increased eIF2α, ATF4 and CHAC1, CHAC1 degraded GSH. | 97. | |
| ATF4-CHOP-CHAC1 | Induction of ferroptosis in Burkitt's Lymphoma. | The ATF4-CHOP-CHAC1 axis degraded intracellular GSH and up-regulated CHAC1. | 93. | |
| ATF4-SLC7A11 | Inhibition of ferroptosis in human gliomas. | ATF4 activation elevated SLC7A11. | 100, 233. | |
| ATF4-CHOP | Induction of ferroptosis in DIR injury. | The activation of ATF4-CHOP produced ERS and interacted with ROS in ferroptosis. | 94. | |
| NOX4 | TAZ-EMP1-NOX4 | Induction of ferroptosis in renal cell carcinoma. | TAZ up-regulated EMP1, EMP1 increased NOX4 and resulted lipid peroxidation. | 115. |
| TLR4-NOX4 | Induction of ferroptosis in rats with heart failure. | TLR4 knock-down repressed NOX4, which inhibited cell loss. | 104. | |
| Fe2+-NOX4-H2O2 | Induction of ferroptosis in glioma cells. | Fe2+ activated NOX4 resulting in H2O2 and lipid peroxides overproduction. | 105. | |
| EGFR-MAPK-NOX4/GPX4 | Induction of ferroptosis in nonsmall-cell lung cancer cells. | Activated EGFR stimulated MAPK signaling, reduced GPX4 and induced NOX4. | 234. | |
| BECN1 | AMPK-BECN1-SLC7A11 | Induction of ferroptosis in tumor suppression. | AMPK-Mediated BECN1 phosphorylation blocked SLC7A11. | 106, 107. |
| ELAVL1/HuR-BECN1-autophagy | Induction of ferroptosis in hepatic stellate cells. | ELAVL1 triggered autophagy and promoted autophagic ferritin degradation by banding to the AREs of the BECN1 mRNA 3'-UTR. | 108. | |
| YAP/TAZ | E-cadherin-NF2-Hippo-YAP | Induction of ferroptosis in epithelial cells. | E-cadherin activated the intracellular NF2 and Hippo signaling pathway to suppress ferroptosis. | 113. |
| TAZ-ANGPTL4-NOX2 | Induction of ferroptosis in epithelial ovarian cancer. | TAZ-regulated ANGPTL4 sensitized ferroptosis by activating NOX2. | 114. | |
| TAZ-EMP1-NOX4 | Induction of ferroptosis in renal cell carcinoma. | TAZ up-regulated EMP1, EMP1 increased NOX4 and resulted lipid peroxidation. | 115. | |
| NRF2 | NRF2-TGF-β1 | Inhibition of ferroptosis in lung fibrosis. | NRF2 signaling down-regulated TGF-β1 and balanced the ROS level. | 231. |
| NRF2-HO-1 | Inhibition of ferroptosis in non-small-cell lung cancer. | NRF2 rescued HO-1 downregulation. | 124. | |
| STAT3-NRF2-GPX4 | Inhibition of ferroptosis in osteosarcoma cells. | Over-activation of STAT3/NRF2 increased GPX4 activity. | 235. | |
| NRF2-Keap1 | Inhibition of ferroptosis in primary malignant brain tumors. | NRF2-Keap1 signaling upregulated SLC7A11 and amplified glutamate secretion. | 120. | |
| p62-Keap1-NRF2 | Inhibition of ferroptosis in hepatocellular carcinoma cells. | p62 prevented the degradation of NRF2 and enhanced subsequent NRF2 nuclear accumulation via of Keap1 inactivation. | 121. | |
| NRF2/p62-ARE | Resistance to ferroptosis in head and neck cancer. | p62-Keap1 interaction activated NRF2, increased ARE resulting in a decreased labile iron pool. | 123. | |
| ARF-NRF2 | Induction of ferroptosis in tumor suppression. | ARF inhibited NRF2 ability to activate its target genes SLC7A11. | 122. | |
| p53 | p53-USP7-H2Bub1-SLC7A11 | Sensitizing cells to erastin-induced ferroptosis. | p53 negatively regulated H2Bub1by promoting the nuclear translocation of the deubiquitinase USP7 and repressed the expression of SLC7A11. | 128. |
| p53-ALOX12 | Induction of ferroptosis in tumor suppression. | p53 activated ALOX12 indirectly by transcriptional repression of SLC7A11. | 127. | |
| p53-SLC7A11 | Induction of ferroptosis in tumor suppression. | p53 repressed SLC7A11 transcription, reduced cystine uptake, and limited GSH. | 105, 236, 237. | |
| SOCS1-p53 | Induction of ferroptosis in tumor suppression. | SOCS1 activated p53 via both phosphorylation and stabilization. | 238. | |
| p53-STAT1-ALOX15 | Induction of ferroptosis in tumor suppression. | p53 directly activated SAT1, and increased the expression of ALOX15. | 129. |
ATF4, activating transcription factor 4; PERK, protein kinase R-like ER kinase; HSPA5, heat shock 70 kDa protein 5; eIF2α, translation initiation factor 2α; CHOP, C/EBP homologous protein; SLC7A11, solute carrier family 7 member 11; NOX4, NADPH oxidase 4; TAZ, transcriptional coactivator with PDZ-binding motif; EMP, epithelial membrane protein 1; TLR4, Toll-like receptor 4; EGFR, epidermal growth factor receptor; GPX4, glutathione peroxidase 4; AMPK, AMP activated protein kinase; ELAVL1/HuR, ELAV like RNA binding protein 1; YAP, yes-associated protein; NRF2, nuclear factor (erythroid-derived 2)-like 2; TGF-β1, transforming growth factor-β1; HO-1, heme oxygenase-1; STAT3, signal transducer and activator of transcription 3; Keap1, Kelch-like ECH associated protein 1; MAPK, mitogen activated protein kinase; ARE, antioxidant response elements; ARF, alternative reading frame; H2Bub1, monoubiquitination of histone H2B at lysine 120; ALOX12, arachidonate 12-lipoxygenase.