MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C<sup>-/-</sup> mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

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Publication Details

Journal
Nature Communications
Published
2024-09-19
DOI
https://doi.org/10.1038/s41467-024-52537-6
Citations
6
Primary Topic
Ferroptosis and cancer prognosis
Type
article
Field-Weighted Citation Impact
2.51

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article

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Xiaona You, Huirui Wang, Hong‐Xiang Lou, Bo Han et al.
6 citations
Nature Communications
Ferroptosis and cancer prognosis
2.51
article

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Xiaona You, Huirui Wang, Hong‐Xiang Lou, Bo Han, Xiaohui Liu, Xinyi Chen, Mengmeng Wang, Ting Dong, Jingcheng Wang, Yinghui Gao, Mei Qi, Wenru Zhang, Jiaozhen Zhang, Yang Yu
article en
6 citations

Abstract

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C<sup>-/-</sup> mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Nature CommunicationsVol. 15(1)
Shandong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), University of Jinan (CN), Ministry of Education (ME), Qilu Hospital of Shandong University (CN), Institute of Infection and Immunity (CA), University College London (GB)
Shandong University, National Natural Science Foundation of China, Servier
Openalex Percentile: Top 10%
Ferroptosis and cancer prognosis
2.51
DOIOpen Access PDFOpenAlex
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