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Updated: Jun 7, 2026
Cochlear Surface Preparation in the Adult Mouse
Published on: November 6, 2019
Macrophage-mediated immune response aggravates hearing disfunction caused by the disorder of mitochondrial dynamics
Yuan Zhang1,2,3, Xiaolong Fu1,4, Yiyuan Li1
1State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University，87# Dingjiaqiao, Nanjing 210096, China.
Abstract:
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.
Insights
Mitochondrial fusion proteins FAM73a/b deficiency damages inner ear hair cells, causing hearing loss. Subsequent immune responses worsen this damage, but reducing macrophages alleviates hearing loss.
Area of Science:
- Cell Biology
- Neuroscience
- Immunology
Background:
- Mitochondrial dynamics are crucial for cellular health and disease.
- Previous research linked mitochondrial dynamics to immunity and anxiety.
- The role of mitochondrial dynamics in auditory function was unknown.
Purpose of the Study:
- To investigate the impact of mitochondrial dynamics on inner ear auditory function.
- To identify the specific roles of FAM73a and FAM73b in hearing.
- To explore the underlying mechanisms of hearing loss associated with mitochondrial dysfunction.
Main Methods:
- Studied FAM73a/b deficient FVB/N mice.
- Assessed outer hair cell (HC) damage and hearing loss.
- Analyzed oxidative stress, apoptosis, and immune cell activation (macrophages, CD4+ T cells).
- Measured inflammatory cytokine expression (IL-12, IFN-γ).
- Used Clophosome®-A-Clodronate Liposomes to deplete macrophages.
Main Results:
- FAM73a/b deficiency caused HC damage and progressive hearing loss.
- Mitochondrial fusion defects led to oxidative stress and apoptosis in HCs.
- Mutant mice showed increased macrophages, CD4+ T cells, IL-12, and IFN-γ.
- Macrophage depletion significantly alleviated hearing loss in mutant mice.
Conclusions:
- FAM73a/b deficiency impairs mitochondrial function, affecting HC survival.
- The resulting cochlear immune response exacerbates HC damage and hearing loss.
- Targeting macrophages may offer a therapeutic strategy for certain types of hearing loss.
