Fig. 6.

Key regulators of Ferroptosis. Ferroptosis is characterized by the production of lipid peroxidation. This process is positively regulated by iron-mediated reactive oxygen species production (NOX, DPP4, GSL2, TRFC), ACSL4-mediated lipid biosynthesis, and ALOX-mediated lipid peroxidation in cell membranes. On the contrary, the GSH pathway (regulated by GCLC, GPX4, GCLM, SLC7A11, GSS and CDKN1A), FABP3 and FABP7 (Upregulation of fatty-acid-binding protein 3 (FABP3) and fatty-acid-binding protein 7 (FABP7), which promotes fatty-acid uptake and lipid storage, driving the decline of ferroptosis (66)), play a parallel or complementary role in protection against membrane injury. YAP1 is transcriptional regulator in cell density mediated ferroptosis resistance, NFE2L2 maintains cell redox homeostasis by combining with an antioxidant response element in target genes.

Abbreviations: TAZ, Transcriptional coactivator with PDZ-binding motif; YAP, Yes-associated protein 1; TRPC, Transferrin Receptor; FTH1, Ferritin Heavy Chain 1; FTL, Ferritin Light Chain; FECH, Ferrochelatase; NOX, NADPH Oxidase; DPP4, Dipeptidyl Peptidase 4; GSL2, Glutaminase 2; HIF1A, Hypoxia Inducible Factor 1 Subunit Alpha; YAP1, Yes1 Associated Transcriptional Regulator; ATF4, Activating Transcription Factor 4; ALOX, Arachidonate Lipoxygenase; LPCAT3, Lysophosphatidylcholine Acyltransferase 3; ACSL4, Acyl-CoA Synthetase Long Chain Family Member 4; HMOX1, Heme Oxygenase 1; MT1G, Metallothionein 1G; FABP3, Fatty Acid Binding Protein 3; FABP7, Fatty Acid Binding Protein 7; NFE2L2, nuclear factor E2-related factor 2; GPX4, Glutathione Peroxidase 4; GCLM, Glutamate-Cysteine Ligase Modifier Subunit; GCLC, Glutamate-Cysteine Ligase Catalytic Subunit; SLC7A11, Solute Carrier Family 7 Member 11; GSS, Glutathione Synthetase; CDKN1A, Cyclin Dependent Kinase Inhibitor 1A