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

IF 13.6 1区 生物学 Q1 CELL BIOLOGY Protein & Cell Pub Date : 2024-09-01 DOI:10.1093/procel/pwae004
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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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.

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铁蛋白沉积途径的蛋白质组分析揭示了 CEPT1 在抑制铁蛋白沉积中的作用。
铁中毒被认为是一种独特的细胞死亡模式,由过度脂质过氧化和不平衡的细胞代谢驱动。在这项研究中,我们通过蛋白质组分析建立了铁变态反应通路的蛋白质相互作用图谱,并发现胆碱/乙醇胺磷酸转移酶 1(CEPT1)是溶血磷脂酰胆碱酰基转移酶 3(LPCAT3)的相互作用蛋白,它能调节 LPCAT3 蛋白的稳定性。与已知的促进磷脂合成的作用不同,我们发现 CEPT1 可能通过与磷脂酶相互作用并分解某些促进铁变态反应的含多不饱和脂肪酸(PUFA)磷脂来抑制铁变态反应。总之,我们的研究揭示了 CEPT1 在抑制铁凋亡中的一种前所未见的作用。
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来源期刊
Protein & Cell
Protein & Cell CELL BIOLOGY-
CiteScore
24.00
自引率
0.90%
发文量
1029
审稿时长
6-12 weeks
期刊介绍: Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.
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