Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis

Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R. Stockwell, Junjie Chen, Boyi Gan

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Protein Cell ›› 2024, Vol. 15 ›› Issue (9) : 686-703. DOI: 10.1093/procel/pwae004
RESEARCH ARTICLE

Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis

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Abstract

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

Keywords

proteomics / ferroptosis / CEPT1 / LPCAT3

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Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R. Stockwell, Junjie Chen, Boyi Gan. Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis. Protein Cell, 2024, 15(9): 686‒703 https://doi.org/10.1093/procel/pwae004

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2024 The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.
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