Investigation of organelle cooperative zones based on membrane lipids

2022 Fiscal Year Final Research Report

• Project Area: Toward an integrative understanding of functional zones in organelles
• Project/Area Number: 17H06418
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: Hiroyuki Arai 東京大学, 大学院医学系研究科(医学部), 客員研究員 (40167987)
• Co-Investigator(Kenkyū-buntansha): 河野 望 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50451852) ; 向井 康治朗 東北大学, 生命科学研究科, 助教 (90767633)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: シグナル伝達 / 生体膜脂質 / オルガネラ

Outline of Final Research Achievements

The cell biological significance of the organelle zones formed by lipids that are characteristic of the organelle was elucidated. Specifically, we found that phosphatidylserine on recycling endosomes regulates the Hippo-YAP pathway and is involved in cancer cell proliferation. We also found that STING, which is important for innate immune responses, is activated in the lipid raft environment of the Golgi, then ubiquitinated in recycling endosomes and degraded by microautophagy. Furthermore, we found that the membrane environment formed by saturated phosphatidylcholine, cardiolipin, and phosphatidic acid is important for TLR4 response, Cullin3 activation, and IRE1 activation, respectively.

Free Research Field

脂質細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として明らかとなった、オルガネラ膜脂質が形成するオルガネラゾーンは、細胞内オルガネラおよび生体膜脂質の機能について新しい概念を提唱するものであり、学術的意義は大きい。また本研究では、オルガネラゾーンの病態生理的意義にも取り組み、ATP8A1、STINGのシステイン残基など、がんや炎症性疾患に対する新たな治療標的となる分子を見出した。将来的にこれらの分子の、がんや炎症性疾患への医療応用が期待でき、社会的意義も大きい。