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. 2022 Jul 26;13:955069. doi: 10.3389/fimmu.2022.955069

Figure 1.

Figure 1

Diagram about mechanism of ferroptosis. ACSL4, acyl-CoA synthetase long-chain family member 4; CISD1, CDGSH iron sulfur domain 1; DAMPs, damage-associated molecular patterns; DMT1, divalent metal transporter 1; F2-I, isoprostane; FPN, ferroportin; FSP1, ferropsis -suppressor-protein 1; FTH, ferritin heavy chain; FTL, ferritin light chain; FtMt, mitochondrial ferritin; Glu, glutamate; GSH, glutathione; GSSG, oxidized glutathione; GPX4, glutathione peroxidase 4; 4-HNE, 4-hydroxynonenal; HSPA5, heat shock protein family A member 5; HSPB1, heat shock protein beta-1; LOX, lipoxygenase; LPCAT3, lysophosphatidylcholine acyltransferase 3; MAA, malondialdehyde-acetaldehyde; MDA, malonaldehyde; mitoROS, mitochondrial reactive oxygen species; NCOA4, nuclear receptor coactivator 4; NOX2, nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase2; Nrf2, nuclear factor erythroid 2-related factor 2; OXPHOS, oxidative phosphorylation; PL, phospholipids; POR, cytochrome P450 oxidoreductase; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; STEAP3, six-transmembrane epithelial antigen of the prostate 3; TfR1, transferrin receptor 1; VDAC, voltage-dependent anion channels; ZIP8/14, Zinc-Iron regulatory protein family 8/14. There are four main sections in the figure showing the mechanism of ferroptosis. The green squares mainly show the metabolic process of iron after entering the cell, including reduction, storage and release, and then active iron becomes an important factor in promoting lipid peroxidation. The pink squares show the process of lipid peroxidation, including the binding of PUFAs and PL, followed by the peroxidation of this complex by ROS and the release of downstream products. The yellow squares show the role of the cellular antioxidant system. GPX4 is the only enzyme that can reduce lipid peroxides, whose inactivation is thought to be the central part of ferroptosis. The content in the dark blue background shows the major changes in mitochondria during ferroptosis, including morphological changes and biochemical reactions. These processes can be modulated by several regulatory factors. The result of ferroptosis is cell rupture and the release of DAMPs.