Elucidation of the mechanism underlying the organization and multiple functions of the MAM

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02439
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TAGAYA MITSUO 東京薬科大学, 生命科学部, 教授 (30179569)
• Co-Investigator(Kenkyū-buntansha): 井上 弘樹 東京薬科大学, 生命科学部, 講師 (10294448) ; 若菜 裕一 東京薬科大学, 生命科学部, 助教 (90635187)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: syntaxin 17 / 小胞体 / ミトコンドリア / オートファジー / 脂肪滴 / インフラマソーム

Outline of Final Research Achievements

Syntaxin17 (Stx17) is localized　in the MAM（mitochondria-associated membrane) and exhibits various functions in response to nutrient situation by binding to different partners. In this study, we obtained the following observations about Stx17. (1) The function of Stx17 is regulated by MAP1B-LC1. (2) Stx17 facilitates lipid droplet formation by regulating the localization of ACSL3, an acyl-CoA synthase involved in lipid droplet formation. The raft structure, which is a membrane microdomain enriched in cholesterol and sphingolipids, is important for the interaction between Stx17 and ACSL3 as well as lipid droplet formation. (3) Stx17 regulates the localization of PGAM5, a protein phosphatase for Drp1, to promote mitochondrial division, and both Stx17 and PGAM5 participate in PINK1-Parkin-mediated mitophagy. (4) Stx17 contributes to the formation of NLRP3 inflammasome

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

小胞体とミトコンドリアの接触領域は、様々な細胞現象（例えば、脂質合成、オートファジー、炎症を惹起するインフラマソームの形成）が起こる場所であり、また、パーキンソン病や糖尿病等の病気の発症とも密接に関連する。この接触領域においてStx17は重要な役割を有しており、このタンパク質の機能の解明が進むことによって、細胞機能の理解が大きく進んだ。更なる発展によって関連する疾患の解明につながることが期待される。