Study on the role of very-long-chain fatty acids in maintaining genome stability

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22389
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Hiraoka Yasushi 大阪大学, 生命機能研究科, 教授 (10359078)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 超長鎖脂肪酸 / 染色体 / ゲノム

Outline of Final Research Achievements

Very long-chain fatty acids are fatty acids with more than 21 carbon chains. Despite being present in only a few percent of total fatty acids, very-long-chain fatty acids have important physiological functions that cannot be replaced by long-chain fatty acids. However, their functions within a cell remain unclear. This study aimed to clarify the intracellular function of very-long-chain fatty acids. In particular, our research focused on the function of the very-long-chain fatty acids on the maintenance of the nuclear envelope and chromatin structure. Our study clarified that very long chain fatty acid synthase and its activity play an important role in the formation and maintenance of the nuclear envelope structure, which is required for genomic stability. Furthermore, it clarified that the nuclear envelope protein Lem2 and ER protein Lnp1 is important for maintaining the boundary between the nuclear envelope and the endoplasmic reticulum membrane.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

超長鎖脂肪酸は、総脂肪酸量のわずか数%しか存在しないにもかかわらず、長鎖脂肪酸には代替できない重要な生理的な働きがある。そのひとつが皮膚のバリアー機能である。超長鎖脂肪酸はセラミド（スフィンゴシンと脂肪酸が結合したもの）として皮膚の脂質膜に含まれることが知られている。しかし、細胞内での、超長鎖脂肪酸の局在や機能など多くの問題が謎のままであった。本研究により、皮膚のない生物である分裂酵母でも、超長鎖脂肪酸が存在し、生存に必須の働きをすることが分かった。さらに、その合成酵素は核膜やER膜に存在し、その活性は、核膜構造の維持を通して、ゲノムの安定維持に働くことが分かった。