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. 2022 Mar 3;10:806081. doi: 10.3389/fcell.2022.806081

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Copyright © 2022 Zhang, Qu, Chen, Luo, Chen, Xiao, Ding, Zhao, Lu, Chen and Yu.

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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Proposed scheme for the underlying mechanisms of atorvastatin-induced muscular cell ferroptosis. Atorvastatin suppressed the Nrf2, which would, in turn, inhibit the expression of System xc− (SLC7A11) and GPx4 (especially the mitochondrial GPx4), leading to a severe damage to the antioxidant system of ferroptosis. Consistently restraining of System xc− (SLC7A11) brought on GSH depletion, which would exaggerate to the dysfunction of GPx4 as well. The GPx4 enzyme catalyzes the transformation of GSH to GSSG and at the meantime decreases the toxic peroxide to non-toxic hydroxy compounds to protect the structure and function of the cell membrane against peroxides.