Fig. 1. Ferroptosis inducing pathways.

Iron enters the cell via TfR1 or DMT1 and is exported by FPT. DMT1 uptakes Fe²⁺ and requires CYDRB1 to reduce Fe³⁺. When inside the cell, iron binds to ferritin, which can be degraded by a lysosomal activity known as ferritinophagy. Non-ferritin iron can then react with O₂ molecule, e.g., H₂O₂ the by-products of this reaction then reacts with PUFAs forming lipid peroxides. System-xc^- imports cysteine and exports glutamate. Cysteine is used in the synthesis of GSH, which, together with GPX4, reduces lipotoxicity. Glutamate participates in glutaminolysis. GSH can be inhibited by downstream metabolites of glutaminolysis. An increase of iron or inhibition of GSH/GPX4 results in ferroptosis. TfR1 Transferrin receptor protein 1, DMT1 divalent metal transporter, FPT ferroportin, CYDRB1 Cytochrome B Reductase 1, PUFAs short for polyunsaturated fats, GSH Glutathione, GSSG Glutathione disulfide, GPX4 Glutathione Peroxidase 4, LOX Lysyl Oxidase.