Macrophage-mediated immune response aggravates hearing disfunction caused by the disorder of mitochondrial dynamics in cochlear hair cells

Yuan Zhang, Xiaolong Fu*, Yiyuan Li, Wen Li, Guodong Hong, Siwei Guo, Yu Xiao, Ziyi Liu, Shuqin Ding, Xiuli Bi, Fanglei Ye*, Jin Jin*, Renjie Chai*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

8 引用 (Scopus)

摘要

Mitochondrial dynamics is essential for maintaining the physiological function of the mitochondrial network, and its disorders lead to a variety of diseases. Our previous study identified mitochondrial dynamics controlled anti-tumor immune responses and anxiety symptoms. However, how mitochondrial dynamics affects auditory function in the inner ear remains unclear. Here, we show that the deficiency of FAM73a or FAM73b, two mitochondrial outer membrane proteins that mediate mitochondrial fusion, leads to outer hair cells (HCs) damage and progressive hearing loss in FVB/N mice. Abnormal mitochondrial fusion causes elevated oxidative stress and apoptosis of HCs in the early stage. Thereafter, the activation of macrophages and CD4+ T cell is found in the mutant mice with the increased expression of the inflammatory cytokines IL-12 and IFN-γ compared with control mice. Strikingly, a dramatically decreased number of macrophages by Clophosome®-A-Clodronate Liposomes treatment alleviates the hearing loss of mutant mice. Collectively, our finding highlights that FAM73a or FAM73b deficiency affects HCs survival by disturbing the mitochondrial function, and the subsequent immune response in the cochleae worsens the damage of HCs.

源语言英语
页(从-至)1137-1151
页数15
期刊Human Molecular Genetics
32
7
DOI
出版状态已出版 - 1 4月 2023
已对外发布

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