Functional interaction of nuclear lipid droplets and invagination of nuclear membrane

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Nagoya University
• Principal Investigator: Ohsaki Yuki 名古屋大学, 医学系研究科, 准教授 (00378027)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 脂肪滴 / 中性脂質 / 核内構造体 / PML

Outline of Final Research Achievements

Lipid droplets (LD), composed of neutral lipids and a phospholipid monolayer, are formed not only in the cytoplasm but in the nucleoplasm in some types of cells. The purpose of this research is to clarify biogenesis mechanism and functions of nuclear LD. We found in hepatic cells, lipoprotein precursors excessively formed in the ER lumen can be spread through the continues luminal space of nuclear membrane as well as nucleoplasmic reticulum (NR), an invagination of inner nuclear membrane, then the luminal precursors become nucleoplasmic LDs after partial rupture of NR membrane. We also found that nuclear LDs are more formed particularly under ER stress, and the surface of nuclear LDs function as a platform in which CCTalpha, a rate-limiting enzyme of de novo phosphatidylcholine (PC) synthesis, is activated and cellular PC synthesis is upregulated. Further, we identified that PLIN3 can bind to nuclear LDs competitively with CCTalpha and work as an endogenous inhibitor of PC synthesis.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、肝細胞には種々のストレス下に晒された際に核内脂肪滴を用いてリン脂質合成・生体膜形成を増強させ、小胞体機能を回復し細胞障害を軽減する機構が備わることを示唆する。肝障害や肝再生時には核内脂肪滴を増強してリン脂質合成を促すことにより、あるいは肝がん細胞においては核内脂肪滴でのリン脂質合成と細胞増殖を抑制することにより、それぞれの新たな治療法に繋がる基礎的知見となった。また本研究の成果は、脂肪滴が蛋白質代謝や遺伝子発現制御など様々な反応の場となる新たな核内構造体である可能性を、医学生物学および生物物理学など複合的な学術領域に提示したといえ、学術的価値は高いと考えられる。