Functional elucidation of the endoplasmic reticulum-mitochondria encounter structure (ERMES) complex

• Project/Area Number: 16K18534
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Toyama Prefectural Institute for Pharmaceutical Research (2019); Yamagata University (2016-2018)
• Principal Investigator: Kojima Rieko 富山県薬事総合研究開発センター, その他部局等, 主任研究員 (60769652)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: オルガネラコンタクト / ERMES / 脂質輸送 / リン脂質 / ミトコンドリア / オルガネラコンタクトサイト

Outline of Final Research Achievements

Recent studies have shown that different organelles physically bind to each other to form an organelle contact site. Organelle contacts are physiologically important because they are associated with diseases such as neurodegenerative diseases, but their functions are not well understood. In this study, we investigated the function of the ERMES complex that physically binds mitochondria to endoplasmic reticulum (ER) and revealed that the ERMES complex plays an important role in transporting phospholipids between mitochondria and ER. We also showed that the ERMES complex is functionally related to the degree of lipid unsaturation.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアと小胞体間のオルガネラコンタクトは，神経変性疾患等の病気とも深く関わっていることが知られているため，オルガネラコンタクトの機能の理解を深めることは，これらの病気のメカニズム解明や将来的な治療へと結びつく可能性があり，重要な研究であると考えられます。

Research Products

• [Journal Article] Crystallization and Biophysical Approaches for Studying the Interactions Between the Vps4-MIT Domain and ESCRT-III Proteins (2019)
  • Author(s): Obita Takayuki、Kojima Rieko、Mizuguchi Mineyuki
  • Journal Title: Methods Mol Biol. Volume: 1998 Pages: 175-187
  • DOI: 10.1007/978-1-4939-9492-2_13
  • ISBN: 9781493994915, 9781493994922
  • Peer Reviewed
• [Journal Article] Advanced In Vitro Assay System to Measure Phosphatidylserine and Phosphatidylethanolamine Transport at ER/Mitochondria Interface (2019)
  • Author(s): Tamura Yasushi、Kojima Rieko、Endo Toshiya
  • Journal Title: Methods Mol Biol. Volume: 1949 Pages: 57-67
  • DOI: 10.1007/978-1-4939-9136-5_6
  • ISBN: 9781493991358, 9781493991365
  • Peer Reviewed
• [Journal Article] Maintenance of Cardiolipin and Crista Structure Requires Cooperative Functions of Mitochondrial Dynamics and Phospholipid Transport (2019)
  • Author(s): Kojima Rieko、Kakimoto Yuriko、Furuta Shiina、Itoh Kie、Sesaki Hiromi、Endo Toshiya、Tamura Yasushi
  • Journal Title: Cell Reports Volume: 26 Issue: 3 Pages: 1372-1372
  • DOI: 10.1016/j.celrep.2018.12.070
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system (2018)
  • Author(s): Kakimoto Yuriko、Tashiro Shinya、Kojima Rieko、Morozumi Yuki、Endo Toshiya、Tamura Yasushi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 6175-6175
  • DOI: 10.1038/s41598-018-24466-0
  • Peer Reviewed / Open Access
• [Journal Article] Structure?function insights into direct lipid transfer between membranes by Mmm1?Mdm12 of ERMES (2017)
  • Author(s): Kawano Shin、Tamura Yasushi、Kojima Rieko、Bala Siqin、Asai Eri、Michel Agn?s H.、Kornmann Beno?t、Riezman Isabelle、Riezman Howard、Sakae Yoshitake、Okamoto Yuko、Endo Toshiya
  • Journal Title: The Journal of Cell Biology Volume: 217 Issue: 3 Pages: 959-974
  • DOI: 10.1083/jcb.201704119
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Crystal Structure of Human General Transcription Factor TFIIE at Atomic Resolution (2016)
  • Author(s): Miwa, K., Kojima, R., Obita, T., Ohkuma, Y., Tamura, Y., and Mizuguchi, M.
  • Journal Title: JOURNAL OF MOLECULAR BIOLOGY Volume: 428 Issue: 21 Pages: 4258-4266
  • DOI: 10.1016/j.jmb.2016.09.008
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of multi-copy suppressors for endoplasmic reticulum-mitochondria tethering proteins in Saccharomyces cerevisiae. (2016)
  • Author(s): Kojima R. Kajiura S. Sesaki H. Endo T. Tamura Y.
  • Journal Title: FEBS Letters Volume: 590 Issue: 18 Pages: 3061-3070
  • DOI: 10.1002/1873-3468.12358
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro. (2016)
  • Author(s): Kojima. R. Endo T. and Tamura Y.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 30777-30777
  • DOI: 10.1038/srep30777
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural Fine-Tuning of MIT-Interacting Motif 2 (MIM2) and Allosteric Regulation of ESCRT-III by Vps4 in Yeast (2016)
  • Author(s): Kojima, R., Obita, T., Onoue, K., Mizuguchi., M.
  • Journal Title: J Mol Biol. Volume: 428(11) Issue: 11 Pages: 2392-2404
  • DOI: 10.1016/j.jmb.2016.04.007
  • Peer Reviewed
• [Presentation] ミトコンドリア・小胞体間コンタクトサイトの数を制御する分子メカニズムの解明 (2019)
  • Author(s): 柿元百合子, 小島理恵子, 遠藤斗志也, 田村康
  • Organizer: 第19回日本蛋白質科学会年会/第71回日本細胞生物学会大会
• [Presentation] ミトコンドリア局在型CDP-DAG合成酵素Tam41の結晶化 (2019)
  • Author(s): 木村啓介, 小島理恵子, 遠藤斗志也, 田村康
  • Organizer: 第19回日本蛋白質科学会年会/第71回日本細胞生物学会大会
• [Presentation] ERMES数を制御する分子メカニズムの解明 (2019)
  • Author(s): 柿元百合子, 小島理恵子, 新名真夏,遠藤斗志也, 田村康
  • Organizer: 日本生化学会大会東北支部第85回例会
• [Presentation] カルジオリピン量の維持には正常なクリステ構造が必要である (2017)
  • Author(s): 小島 理恵子，伊藤 喜重, 瀬崎 博美，遠藤 斗志也， 田村 康
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 新規のin vitro PS輸送実験を用いたERMES複合体のリン脂質輸送機能の解明 (2016)
  • Author(s): 小島理恵子, 遠藤斗志也, 田村康
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス
  • Year and Date: 2016-09-25
• [Presentation] 小胞体膜タンパク質 Ilm1 はミトコンドリア小胞体間リン脂質輸送を負に制御する (2016)
  • Author(s): 古田詩唯奈, 小島理恵子, 田村康, 遠藤斗志也
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス
  • Year and Date: 2016-09-25