Exploration of phenomena indicative of mitochondrial dysfunction and its applications

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H03180
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kyushu University
• Principal Investigator: Matsushima Yuichi 九州大学, 医学研究院, 助教 (20571342)
• Co-Investigator(Kenkyū-buntansha): 瀬戸山 大樹 九州大学, 大学病院, 助教 (30550850) ; 相原 正宗 九州大学, 大学病院, 臨床検査技師 (30748843) ; 内海 健 九州大学, 医学研究院, 教授 (80253798)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ミトコンドリア / タンパク質凝集

Outline of Final Research Achievements

It has been suggested that mitochondrial dysfunction triggers the onset of aging and lifestyle-related diseases. However, a simple and reproducible method to evaluate mitochondrial dysfunction such as decreased ATP synthesis has not been found. In this study, we focused on LONP1, a protease localized in the mitochondrial matrix, and found that LONP1 functions in a manner dependent on ATP hydrolysis and that its dysfunction causes the accumulation of protein aggregates in the mitochondrial matrix. This indicates that the accumulation of protein aggregates may be an indicator of abnormal mitochondrial function accompanied by a decrease in the amount of ATP in the mitochondrial matrix.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はミトコンドリア機能異常をタンパク質凝集体の蓄積を介して評価するというこれまでとは全く異なるミトコンドリア機能解析法の可能性を示したものである。また。LONP1の機能低下に伴うミトコンドリアマトリクスでのタンパク質凝集体の蓄積はLONP1の変異が引き起こす「脳・眼・歯・耳介・骨格症候群」でも観察され現象であり、本研究成果は「脳・眼・歯・耳介・骨格症候群」の病態解明にも寄与する。