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. 2022 Jul 31;11(8):1504. doi: 10.3390/antiox11081504

Figure 1.

Figure 1

The signaling pathways and regulatory mechanisms of lipid-peroxidation-mediated ferroptosis. The lines and text in red denote ferroptosis inducers, while the lines and text in blue denote ferroptosis inhibitors. System Xc- consists of SLC7A11 and SLC3A2. SLC1A5 is a glutamine importer [62]. GSH is synthesized from Cys, Glu, and Gly in two steps: firstly, the ATP-dependent cytosolic enzyme GCL synthesizes γ-glutamyl-cysteine from Gln and Cys; secondly, GSS synthesizes GSH from γ-glutamyl-cysteine and Gly. GPX4 and GSH can prevent lipid ROS accumulation. GSH reductase utilizes NADPH to reduce GSSG to GSH. ACSL4 utilizes AA and AdA to synthesize AA-CoA and AdA-CoA. LPCAT3 catalyzes ACSL4-synthesized AA-CoA and AdA-CoA into PE species. Lipoxygenase oxidizes PE species into PUFA-OOHs. Lastly, GPX4 catalyzes the lipid hydroperoxides PUFA-OOHs into lipid alcohols PUFA-OH.