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1 Although sharing the more common features of ferroptosis, RSL3-mediated ferroptosis does not include decreased levels of cellular GSH

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The synthesis of GPX4 begins with cystine being transported into cells via the system Xc⁻ transporter, a heterodimer of SLC7A11 and SLC3A2 embedded in the cell membrane, followed by intracellular conversion of cystine to cysteine, which combines with glutamate and glycine to form glutathione (GSH) which serves as the substrate for GPX4, a selenoprotein that utilizes its intrinsic GSH to reduce cytotoxic lipid hydroperoxides into non-toxic lipid alcohols, thereby inhibiting ferroptosis [93, 94]