The oxidoreductases POR and CYB5R1 catalyze lipid peroxidation to execute ferroptosis

Youwei Ai; Bo Yan; Xiaodong Wang

doi:10.1080/23723556.2021.1881393

The oxidoreductases POR and CYB5R1 catalyze lipid peroxidation to execute ferroptosis

Mol Cell Oncol. 2021 Feb 8;8(2):1881393. doi: 10.1080/23723556.2021.1881393. eCollection 2021.

Authors

Youwei Ai^{1

2}, Bo Yan¹, Xiaodong Wang^{1

2}

Affiliations

¹ National Institute of Biological Sciences, Beijing, China.
² Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.

Abstract

Our recent study showed that two oxidoreductases - NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1) - transfer electrons to oxygen to generate hydrogen peroxide (H₂O₂). H₂O₂ then reacts with ferrous iron, generating hydroxyl radicals that cause peroxidation of polyunsaturated-fatty-acid chains of membrane phospholipids, resulting in plasma membrane rupture and ferroptosis.

Keywords: CYB5R1; FSP1; Ferroptosis; GPX4; H2O2; POR; PUFA; hydroxyl radicals; lipid peroxidation; oxidoreductase.

Grants and funding

Y.A. was supported by the China Postdoctoral Innovation Talent Support Program. This work was supported by institutional grants from the Chinese Ministry of Science and Technology and the Beijing Municipal Commission of Science and Technology.