Fig. 1.

Mechanisms regulating ferroptosis. Specific mechanisms regulating ferroptosis, including various inducers and inhibitors. System X_c⁻ transports extracellular Cys2 into the cell and transports intracellular Glu outside the cell, and then Cys2 is used to synthesize GSH. GPX4 combines with PUFA-OH to reduce reactive oxygen species generation and ultimately inhibit lipid peroxidation. Extracellular Fe³⁺ binds to the iron transporter and enters the cell through TFR1 on the cell membrane. Next, Fe³⁺ is reduced to Fe²⁺ and combined with reactive oxygen species to participate in lipid peroxidation, and finally induce ferroptosis. ⊖ indicates inhibition, and ⊕ indicates induction, System X_c⁻ a glutamate/cystine antiporter; Shmt1/2, serine hydroxymethyltransferase ½, GSS glutathione synthase, GSH glutathione, GSSH glutathione persulfide, GPX4 glutathione peroxidase 4, GSR glutathione reductase, ALOX5 arachidonate lipoxygenase 5, NCOA4 nuclear receptor co-activator 4, SLC7A11 solute carrier family 7 member 11, SLC3A2 solute carrier family 3 member 2, SLC1A5 solute carrier family 1 member 5, TFR1 transferrin receptor 1, VDAC2/3 voltage-dependent anion channel 2/3, ATG5/7 autophagy-related protein 5/7, Nrf2 nuclear factor E2-related factor 2, NFE2L2 nuclear factor, erythroid 2-like 2, ATF4 activating transcription factor 4, lncRNA long noncoding RNAs, miRNA microRNA, PUFA polyunsaturated fatty acid, BSO buthionine sulfoximine, RRM2 ribonucleotide reductase M2, FBW7 F-box and WD repeat domain-containing 7, NR4A1 nuclear receptor subfamily 4 group A member 1, SCD1 stearoyl-CoA desaturase 1, RSL3 Ras-selective lethal 3, FANCD2 Fanconi anaemia complementation group D2, FINO2 1,2-dioxolane, ML162 (S)-enantiomer, DPI diphenylene iodonium, LONP1 mitochondrial Lon protease 1, CoQ10 coenzyme Q10, ESCRT endosomal sorting complex required for transport, AIFM2 apoptosis-inducing factor mitochondria-associated 2