Yilin Sun1  · Chunying Liu2  · Yakun Liang3  · An Lv2  · Wang Nie1  · Shuyue Bao1  · Xiaoyi Li4  · Jing Zhou4  · Weimin Tong5,6 · Yong Tao1  · Xueling Wang4  · Tingting Dong4

1 Department of Otolaryngology‑Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China 

2 Center for Experimental Animal Research, Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing 100005, China 

3 Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China 

4 Biobank of Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China 

5 Department of Pathology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100005, China 

6 Neuroscience Center and Molecular Pathology Research Center, Chinese Academy of Medical Sciences, Beijing 100005, China

Abstract

Auditory neuropathy (AN) is a sensorineural hearing loss that impairs speech perception, but its mechanisms and treatments remain limited. Mic60, essential for the mitochondrial contact site and cristae organizing system, is linked to neurological disorders, yet its role in the auditory system remains unclear. We demonstrate that Mic60^+/− mice develop progressive hearing loss from 6 months of age, with reduced auditory brainstem response amplitudes despite preserved outer hair cell function, consistent with AN. Mitochondrial abnormalities in spiral ganglion neurons (SGNs) emerge by 3 months, followed by mitochondrial loss and SGN degeneration, indicating progressive auditory neuron dysfunction. In vitro, Mic60 deficiency disrupts mitochondrial respiration, reversible by N-acetylcysteine (NAC). NAC treatment preserves mitochondrial integrity and rescues hearing by enhancing mitophagy. Our findings establish Mic60^+/− mice as an AN animal model, highlight the role of Mic60 in the mitochondria of primary auditory neurons, and identify NAC as a potential AN treatment.

Keywords

Mic60; Mitochondria; Auditory neuropathy; Mitophagy; Antioxidant; N-acetylcysteine

[Springerlink]