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Cited by 617

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Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1

Open access
Yan, Bo, Ai, Youwei, Sun, Qi, Ma, Yan, Cao, Yang, Wang, Jiawen, Zhang, Zhiyuan, Wang, Xiaodong·2021·Molecular Cell

Abstract

Ferroptosis is a form of necrotic cell death caused by iron-dependent peroxidation of polyunsaturated phospholipids on cell membranes and is actively suppressed by the cellular antioxidant systems. We report here that oxidoreductases, including NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1), transfer electrons from NAD(P)H to oxygen to generate hydrogen peroxide, which subsequently reacts with iron to generate reactive hydroxyl radicals for the peroxidation of the polyunsaturated fatty acid (PUFA) chains of membrane phospholipids, thereby disrupting membrane integrity during ferroptosis. Genetic knockout of POR and CYB5R1 decreases cellular hydrogen peroxide generation, preventing lipid peroxidation and ferroptosis. Moreover, POR knockdown in mouse liver prevents ConA-induced liver damage. Ferroptosis, therefore, is a result of incidental electron transfer carried out by POR/CYB5R1 oxidoreductase and thus needs to be constitutively countered by the antioxidant systems.

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Metadata

Authors
Yan, B., Ai, Y., Sun, Q., Ma, Y., Cao, Y., Wang, J., Zhang, Z., & Wang, X.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2021-01
Volume
81
Issue
2
Pages
355-369.e10
ISSN
1097-2765 (ISSN-L)
OpenAlex
W3111227304
Cited by
617
References
14
FWCI
31.40
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. https://app.cochat.ai/papers/10.1016/j.molcel.2020.11.024
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Yan, B., Ai, Y., Sun, Q., Ma, Y., Cao, Y., Wang, J., Zhang, Z., & Wang, X. (2021). Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Molecular Cell. https://doi.org/10.1016/j.molcel.2020.11.024

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