2022 Fiscal Year Final Research Report

A study of the role of mitophagy in hearing disorder

Research Project

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Project/Area Number	20K21646
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	The University of Tokyo
Principal Investigator	Yamasoba Tatsuya 東京大学, 医学部附属病院, 教授 (60251302)
Co-Investigator(Kenkyū-buntansha)	木下淳東京大学, 医学部附属病院, 助教 (10755648) 樫尾明憲東京大学, 医学部附属病院, 准教授 (20451809) 鴨頭輝東京大学, 医学部附属病院, 助教 (30807152) 藤本千里東京大学, 医学部附属病院, 講師 (60581882)
Project Period (FY)	2020-07-30 – 2023-03-31
Keywords	ミトコンドリア / オートファジー / 内耳 / 加齢性難聴 / ミトコンドリア病 / 酸化ストレス
Outline of Final Research Achievements	In the HEI-OC1 cell senescence model, mitochondrial respiratory capacity, ATP production rate, mitochondrial membrane potential, mitochondrial fusion and motility were impaired, and the expression of sirtuin 1 and PGC-1α was decreased. PQQ pretreatment showed a protective effect against these. In C57BL/6 mice showing age-related hearing loss, PQQ had a protective effect, such as amelioration of hearing loss, prevention of the loss in the number of the hair cells, the spiral ganglion cells, and ribbon synapses. CBA mice treated with GeO2-containing food developed severe to profound hearing loss and severe degeneration of the stria vascular in the cochlea. These mice treated with GeO2 showed reduction of gene expression in 16 categories associated with mitochondria, mitochondrial inner membrane, and mitochondrial electron transport chain. Three antioxidants, taurine, coenzyme Q10, and hydrogen water, showed marked preventive effects against GeO2-induced cochlear damage.
Free Research Field	耳鼻咽喉科学
Academic Significance and Societal Importance of the Research Achievements	内耳細胞の老化モデルではミトコンドリア呼吸能、ATP産生速度、ミトコンドリア膜電位・融合・運動性が障害され、sirtuin 1およびPGC-1αの発現減少が関与することが初めて示された。また加齢性難聴が酸化還元酵素の補酵素であるpyrroloquinoline quinone（PQQ）により予防できることがin vivoでも示されたこと、GeO2による内耳障害ではミトコンドリア関連遺伝子発現が減少して障害が起きるが、抗酸化物質によりそれも予防できることを示したことで、加齢性難聴やミトコンドリア病に伴う難聴の予防や治療法の開発に貢献すると期待される。