Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pa...Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。展开更多
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,i...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.展开更多
基金supported in part by the National Key Research and Development Program of China(2019YFA080703)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-002,2021-I2M-020)Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project#2021ZD0201100 Task 1#2021ZD0201101。
文摘Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。
基金National Natural Science Foundation of China(82201275,82371144,82371145)Interdisciplinary Program of Shanghai Jiao Tong University(YG2022QN064)Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)。
文摘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.
