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DMT1 then mediates the transport of Fe 2+ from the endosome to the cell labile iron pool (LIP) ( Nuclear receptor coactivator 4 (NCOA4) binds to ferritin and mediates its delivery to autophagosomes ( 2+ participates in a series of physiological cell processes, including the generation of ROS through Fenton reactions, which further promotes lipid peroxidation ( 2.3 Ferroptosis defense mechanisms 2.3.1 System X c /GSH/GPX4 axis The System X c /GSH/GPX4 axis, DHODHubiquinol (CoQH 2 ) system, FSP1CoQ10 axis, GTP cyclohydrolase-1 (GCH1)tetrahydrobiopterin (BH4) axis, and sex hormones can inhibit ferroptosis, and the inhibition of related molecular pathways is an important strategy to induce ferroptosis in tumor cells ( c is a heterodimeric amino-acid transporter located on the cell membrane and consisting of two subunits: SLC3A2 and SLC7A11 ( c /GSH/GPX4 axis and can be roughly divided into four classes based on their targets: class-1 FINs such as erastin inhibit SLC7A11, class-2 FINs such as RSL3 and ML162 inhibit GPX4 enzyme activity, class-3 FINs such as FIN56 deplete GPX4 and CoQ10, and class-4 FINs induce lipid peroxidation ( 2.3.2 Other ferroptosis-associated axes Although GSH/GPX4, ACSL4, and PUFA are the main factors required for ferroptosis, exogenous oxygen radicals generated by photodynamic therapy (PDT) can directly peroxidize PUFAs and initiate lipid autoxidation, triggering ferroptosis-like cell death by means independent of LOXs and ACSL4 ( NFE2L2/NRF2 defends against oxidative stress in cells, and various ferroptosis-related proteins, including those related to cellular iron metabolism and GSH metabolism, are its targets ( c /GSH/GPX4 axis, including SLC7A11, GSH synthase, and GPX4, which inhibits ferroptosis ( in vivo and in vitro ( A group of genes that antagonize iron-dependent cell death, including GCH1 and its metabolic derivatives BH4/dihydrobiopterin (BH2), has been identified, and BH4/BH2 synthesis-induced lipid remodeling have been found to inhibit ferroptosis by selectively preventing the consumption of two polyunsaturated acyl-tailed phospholipids ( 2 (a radicular-trapping antioxidant with anti-ferroptotic activity) ( 2 , supporting the hypothesis that G3P in mitochondria also acts as an RTA to inhibit ferroptosis ( 2.3.3 Regulation of ferroptosis and other types of cell death by p53 p53 is an important tumor suppressor that functions as a transcription factor (65)
