Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis
Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis
Abstract Tissue damage elicits a rapid innate immune response that is essential for efficient wound healing and survival of metazoans. It is well known that p38 MAPK kinase, TGF-β, and hemidesmosome signaling pathways have been involved in wounding-induced innate immunity in C. elegans. Here, we find that loss of function of ATFS-1 increased innate immune response while an elevated level of mitochondrial unfolded protein response (mitoUPR) inhibits the innate immune response upon epidermal wounding. Epidermal wounding triggers the nucleus export of ATFS-1 and inhibits themitoUPR in C. elegans epidermis. Moreover, genetic analysis suggests that ATFS-1 functions upstream of the p38 MAP kinase, TGF-β and DAF-16 signaling pathways in regulating AMPs induction. Thus, our results suggest that the mitoUPR function as an intracellular signal required to fine-tune innate immune response after tissue damage. Highlights—ATFS-1 inhibits the wounding-induced innate immune response in C. elegans—mitoUPR inhibits wounding-induced innate immune response—Epidermal wounding induces downregulation of ATFS-1 in the epidermis—mitoUPR acts upstream of p38MAPK and TGF-β pathways to regulate innate immunity
Zhou Hengda、Ren Xuecong、Wang Yuanyuan、Xu Suhong、Zhao Jianzhi、Fu Hongying
The Zhejiang University-University of Edinburgh InstituteCenter for Stem cell and Regenerative Medicine and Department of Cardiology of the second affiliated hospital, Zhejiang University School of MedicineCenter for Stem cell and Regenerative Medicine and Department of Cardiology of the second affiliated hospital, Zhejiang University School of MedicineCenter for Stem cell and Regenerative Medicine and Department of Cardiology of the second affiliated hospital, Zhejiang University School of Medicine||The Zhejiang University-University of Edinburgh InstituteCenter for Stem cell and Regenerative Medicine and Department of Cardiology of the second affiliated hospital, Zhejiang University School of MedicineCenter for Stem cell and Regenerative Medicine and Department of Cardiology of the second affiliated hospital, Zhejiang University School of Medicine
分子生物学细胞生物学遗传学
Innate immune responseEpidermal woundingMitochondrial UPRATFS-1AMPs p38MAPKTGF-βNLPsCaenacins
Zhou Hengda,Ren Xuecong,Wang Yuanyuan,Xu Suhong,Zhao Jianzhi,Fu Hongying.Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis[EB/OL].(2025-03-28)[2025-06-13].https://www.biorxiv.org/content/10.1101/2021.09.19.460990.点此复制
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