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. 2022 Apr 18;61:101502. doi: 10.1016/j.molmet.2022.101502

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© 2022 The Author(s)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

The regulation mechanisms of p62-Keap1-Nrf2 and FSP1 in ferroptosis. During ferroptosis, p62 protein competitively binds to Keap1, and Nrf2 will be released to enhance the subsequent increase of Nrf2 into the nucleus, thereby activating NQO1, HO-1 and FTH1 to participate in iron metabolism and lipid peroxidation. The Nrf2/keap1 pathway can promote the expression of System Xc-under oxidative stress, and SLC7A11 serves as the transcription target of Nrf2. Nrf2 can also inhibit ferroptosis through GPX4 and participate in the pentose phosphate pathway to produce NADPH. FSP1 can inhibit lipid oxidation and ferroptosis through its CoQ oxidoreductase activity.