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Cystine metabolism is a vital segment in the GPX4-dependent ferroptosis pathway and the main factors affecting cystine metabolism include the transsulfuration pathway and/or the methionine cycle ( In addition, the mevalonate pathway also participated in GPX4 activity regulation and isopentenyl pyrophosphate was the core factor regulating the transcription efficiency of GPX4 ( Currently, researchers have demonstrated that lonizing radiation could consume GSH, inhibit GPX4 activity, and induce ferroptosis ( GPX4 Independent Ferroptosis Pathway Although GPX4 is the core molecule of ferroptosis, we have now found other pathways that influence PLOOH synthesis and ferroptosis ( The first is the ferroptosis inhibition protein 1(FSP1) (60), which can reduce the mevalonate pathway produced ubiquinone translate to ubiquinol, suppress production of PLOOH, and eventually inhibit ferroptosis (61), and in addition to activating FSP1 functions, PPAR also regulates the conversion of PL-MUFA to PLOOH by ACSL3-mediated MUFA way

Nat Rev Neurol 19:715736