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2020 Fiscal Year Final Research Report

Studies on the function of the lipid droplet surface

Research Project

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Project/Area Number 18H04023
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionJuntendo University (2019-2020)
Nagoya University (2018)

Principal Investigator

Fujimoto Toyoshi  順天堂大学, 医学(系)研究科(研究院), 特任教授 (50115929)

Co-Investigator(Kenkyū-buntansha) 大崎 雄樹  名古屋大学, 医学系研究科, 准教授 (00378027)
辻 琢磨  順天堂大学, 医学(系)研究科(研究院), 特任助教 (40725628)
Project Period (FY) 2018-04-01 – 2021-03-31
Keywords脂肪滴 / ホスファチジルコリン / 肝細胞 / オートファジー / 核膜 / 小胞体ストレス
Outline of Final Research Achievements

The surface of lipid droplets (LDs) has properties different from other biological membranes and recruit unique proteins. In hepatocytes exposed to the endoplasmic reticulum stress, we discovered that lipids, which are normally secreted as lipoproteins, enter the nucleus and generate nuclear LDs. These nuclear LDs recruit and activate CCTα, an isoform of the enzyme critical for phosphatidylcholine synthesis, thereby contributing to mitigation of the endoplasmic reticulum stress. In cells under starvation, free fatty acids derived from digested self materials generate cytoplasmic LDs. On those LDs, CCTβ3, a different isoform of CCT, is activated, and this helps cells to maintain autophagy and survive for a prolonged time in starvation.

Free Research Field

細胞生物学、解剖学一般

Academic Significance and Societal Importance of the Research Achievements

これまで不明であった肝細胞における核内脂肪滴の形成機構が解明され、CCTα活性化を通じてストレス緩和に寄与することが明らかになった。肝細胞のストレス増悪は脂肪肝などの疾病要因であり、今後、核内脂肪滴を標的とした予防・治療法への展開が期待できる。一方、飢餓時に形成される細胞質脂肪滴はCCTβ3活性化を通じてオートファジーの維持に重要な役割を果たすことが分かった。低栄養状態下の癌細胞生存にはこの機序が関与していると推測され、CCTβ3を標的とした制癌治療の可能性が示された。

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Published: 2022-01-27  

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