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. 2021 Aug 13;9:699304. doi: 10.3389/fcell.2021.699304

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Copyright © 2021 Wang, Wang, Li, Qin and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The regulation mechanism of ferroptosis by ubiquitination. Ferroptosis is tightly relevant to amino acid, iron, and lipid metabolism. Intracellular labile iron is capable of triggering lipid peroxidation to induce ferroptosis. System Xc^– transporter-mediated cystine uptake, which, in concert with GPX4, can reduce the cytotoxic lipid peroxides and inhibit ferroptosis. In addition, FSP1 and DHODH inhibit ferroptosis independent of GPX4. Modulation of these pathways by ubiquitination contributes to ferroptosis regulation.