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

doi:10.1093/procel/pwae004

Protein Cell

2024, Vol. 15

Issue (9) : 686-703 https://doi.org/10.1093/procel/pwae004

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

Xiaoguang Liu¹, Zhen Chen¹, Yuelong Yan¹, Fereshteh Zandkarimi², Litong Nie¹, Qidong Li¹, Amber Horbath¹, Kellen Olszewski^3,⁵, Lavanya Kondiparthi³, Chao Mao¹, Hyemin Lee¹, Li Zhuang¹, Masha Poyurovsky³, Brent R. Stockwell², Junjie Chen^1,⁴(

), Boyi Gan^1,⁴(

)

¹. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
². Department of Biological Sciences and Department of Chemistry, Columbia University, New York, NY 10027, USA
³. Kadmon Corporation, LLC (A Sanofi Company), New York, NY 10016, USA
⁴. The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
⁵. Present address: The Barer Institute, Philadelphia, PA 19104, USA

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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

Corresponding Author(s): Junjie Chen,Boyi Gan

Online First Date: 24 May 2024 Issue Date: 18 September 2024

Cite this article:

Xiaoguang Liu,Zhen Chen,Yuelong Yan, et al. Proteomic analysis of ferroptosis pathways reveals a role of CEPT1 in suppressing ferroptosis[J]. Protein Cell, 2024, 15(9): 686-703.

URL:

https://academic.hep.com.cn/pac/EN/10.1093/procel/pwae004
https://academic.hep.com.cn/pac/EN/Y2024/V15/I9/686

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