Lipid analysis associated with disruption of membrane contact site and stress response

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15798
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Toyama Prefectural Institute for Pharmaceutical Research
• Principal Investigator: Kojima Rieko 富山県薬事総合研究開発センター, その他部局等, 主任研究員 (60769652)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脂質解析 / リン脂質

Outline of Final Research Achievements

The cell contains different functional organelles, such as endoplasmic reticulum and mitochondria, which are surrounded by biological membranes. The composition of lipids, which are the main components of biological membranes, varies among organelles, and their lipid compositions are tightly regulated. However, the mechanisms underlying lipid synthesis, distribution, and transport to appropriate organelles remain largely unexplored. In this study, we demonstrated that a yeast orthologue of neurodegenerative disease-related gene may be involved in the synthesis and transport of intramitochondrial phospholipids. The results of this study may lead to the elucidation of the molecular mechanism and drug discovery for neurodegenerative diseases.

Free Research Field

細胞生物学，生化学

Academic Significance and Societal Importance of the Research Achievements

本研究では，ヒトの神経変性疾患原因遺伝子の酵母オルソログに疾患関連変異を導入すると，ミトコンドリア内リン脂質の異常に加えて，ミトコンドリア形態の異常，呼吸活性低下などが引き起こされ，ミトコンドリア機能不全に陥ることが明らかとなりました。神経変性疾患は，いまだに明確な発症メカニズムは分かっておらず根本的な治療薬も存在しませんが，本研究成果より，分子病態メカニズムの解明や創薬につながる可能性があり，学術的意義，社会的意義は大きいと考えます。