Summary of project PR002309

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002309. The data can be accessed directly via it's Project DOI: 10.21228/M85J9C This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR002309
Project DOI:doi: 10.21228/M85J9C
Project Title:CD9-dependent extracellular vesicles mediate the propagation of ferroptosis
Project Summary:Ferroptosis is a form of regulated cell death that is mediated by accumulation of lipid peroxides. Emerging evidence suggests that ferroptosis as a cell-autonomous event can propagate to surrounding cells. Although a detailed mechanistic understanding of is still lacking, such a propagating feature of ferroptosis has far-reaching implications in developmental and pathological processes. Here, we show that the intercellular transmission of ferroptosis relies on an extracellular vesicle (EV)-dependent transport mechanism. Ferroptotic cells produce massive amounts of EVs carrying death signals. Proteomic analysis reveals that these EVs are CD9 positive and contain major components of the mitogen-activated protein kinase (MAPK) signaling. Further untargeted lipidomics results show that EVs secreted from ferroptotic cells (RSL3-EVs) and control EVs (DMSO-EVs) shared similar lipid composition. EV-transported MAP2K1/2 sensitizes target cells for ferroptosis through the action of peroxisome-proliferator activator receptor gamma (PPARG), a transcription factor that controls expression of various components of ferroptosis defense systems. Perturbation of EV-based transport protects adjacent tissue from ferroptosis in vivo. Our study thus uncovers an EV-dependent intercellular transport mechanism of ferroptosis that is mediated by the MAPK-responsive PPARG pathway.
Institute:Zhejiang University
Department:School of Medicine
Last Name:Li
First Name:Yue
Address:866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China
Email:liyue9104@zju.edu.cn
Phone:(86)18869960769

Summary of all studies in project PR002309

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ST003720 CD9-dependent extracellular vesicles mediate the propagation of ferroptosis Homo sapiens Zhejiang University MS 2026-01-02 1 12 Uploaded data (5.5G)*
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