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Fig 1.

Pathways regulating ferroptosis.

Summary of ferroptosis mechanisms and signaling pathway. Ferroptosis inducers/sensitizers are colored red. Ferroptosis inhibitors are colored green. 2,2-BP, 2,2-bipyridyl; ACSL4, acyl-CoA synthetase long chain family member 4; ALOX, arachidonate lipoxygenase; BHT, butylated hydroxytoluene; CoQ10, coenzyme Q10; CPX, ciclopirox olamine; DFO, deferoxamine; D-PUFA, deuterated polyunsaturated fatty acids; Fer-1, ferrostatin-1; FIN56, ferroptosis inducer 56; FINO2, ferroptosis inducer endoperoxide; GPX4, glutathione peroxidase 4; GSSG, glutathione disulfide; HMG-CoA, β-hydroxy β-methylglutaryl-CoA; IKE, imidazole ketone erastin; LPCAT3, lysophosphatidylcholine acyltransferase 3; PL-PUFA (PE), polyunsaturated-fatty-acid-containing phospholipids; PL-PUFA(PE)-OOH, polyunsaturated-fatty-acid-containing-phospholipid hydroperoxides; PUFA, polyunsaturated fatty acid; ROS, reactive oxygen species; RSL3, RAS-selective lethal 3

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Table 1.

Ferroptosis inducers.

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Table 2.

Ferroptosis inhibitors.

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Table 3.

Key ferroptosis-related genes.

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Fig 2.

Fenton chemistry and lipid peroxidation in ferroptosis.

There are three steps involved in nonenzymatic lipid peroxidation. The first step is the generation of lipid radicals (initiation). The second step is the creation of new lipid radicals (propagation). The final step is termination, either by antioxidants or another radical. PUFA, polyunsaturated fatty acid.

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Fig 3.

Subcellular model of the location of lipid peroxidation in ferroptosis.

The red question marks represent the unsolved mysteries discussed in the article. 4-HNE, 4-hydroxynonenal; MDA, malondialdehyde; PL-PUFA(PE)-OOH, polyunsaturated-fatty-acid-containing-phospholipid hydroperoxides; ROS, reactive oxygen species.

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