Regulation of cellular functions by phospholipids

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: National Institute of Infectious Diseases (2023); Kyushu University (2020-2022)
• Principal Investigator: Miyata Non 国立感染症研究所, 細胞化学部, 室長 (10529093)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ミトコンドリア / リン脂質

Outline of Final Research Achievements

In the present research, we attempted to elucidate the regulatory mechanism of cellular phospholipid biosynthesis and its physiological significance by using mammalian culture cell and yeast systems and revealed the following: (1) Mtochondria-derived phosphatidylethanolamine (PE) has a role in regulation of the cellular energy sensor, AMPK/Snf1 and affects quiescence (G0) entry in yeast. Furthermore, synthetic pathway of mitochondrial PE could be a potential target for therapy against Rb1-deficient cancer cells. (2) the regulatory mechanisms for subcellular localization and abundance of PE-synthesizing enzyme, Psd1 in yeast. (3) Topology of mammalian phosphatidylserine (PS)-synthesizing enzyme, PSS1 in the endoplasmic reticulum membrane.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究を通じ、代表者はリン脂質合成制御機構およびその生理的意義について独創性の高い成果を挙げた。これらの成果は、細胞の環境変化に応じた細胞機能、細胞運命の制御機構の理解に大きく貢献するものと考えられる。さらに本研究で明らかとなった、ミトコンドリア由来PEを介したG0細胞分化制御機構や、Rb1欠損性乳がん細胞の増殖におけるミトコンドリア由来PE依存性は、今後再生医療やがん治療など医療面の発展に貢献するものと考えられる。また、PSS1の膜配向性解析から示唆されたPSS1活性制御機構は、Lenz-Majewski症候群やがんなど、諸疾患の病態、治療法解明に貢献するものと期待される。