Proteomic Analysis of Ferroptosis Pathways Reveals a Role of CEPT1 in Suppressing Ferroptosis

Authors

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

Publication Date

9-1-2024

Journal

Protein Cell

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

Humans, 1-Acylglycerophosphocholine O-Acyltransferase, Ferroptosis, HEK293 Cells, Proteomics, Transferases (Other Substituted Phosphate Groups), proteomics, ferroptosis, CEPT1, LPCAT3

DOI

10.1093/procel/pwae004

PMID

38430542

PMCID

PMC11365556

PubMedCentral® Posted Date

3-2-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes