生物
线粒体
毛细胞
细胞生物学
免疫系统
内耳
细胞凋亡
免疫学
听力损失
氧化应激
线粒体融合
炎症
耳蜗
巨噬细胞
线粒体DNA
神经科学
内分泌学
遗传学
体外
医学
听力学
基因
作者
Yuan Zhang,Xiaolong Fu,Yiyuan Li,Wen Li,Guodong Hong,Siwei Guo,Xiao Yu,Ziyi Liu,Shuqin Ding,Xiuli Bi,Fanglei Ye,Jin Jin,Renjie Chai
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.
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