Analysis of phospholipid-transport mechanism between mitochondria and the endoplasmic reticulum

• Project/Area Number: 25870311
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry; Structural biochemistry
• Research Institution: Nagoya University
• Principal Investigator: TAMURA Yasushi 名古屋大学, 物質科学国際研究センター, 准教授 (50631876)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ミトコンドリア / リン脂質輸送 / カルジオリピン / リン脂質

Outline of Final Research Achievements

Characteristic functions of membrane-bound structures (organelles) in cells are essential for vital activities. Proper phospholipid composition of mitochondrial membranes is required for optimal mitochondrial functions.
In this study, we identified a gene encoding a mitochondrial protein, which genetically interacts with UPS1 as a novel factor involving in phospholipid transport. In addition, by biochemical analyses using recombinant Ups1, we revealed that dynamic interactions between Ups1 and Mdm35 are important for phospholipid transport. These findings would help our understandings in mechanisms of phospholipid transport as well as mitochondrial biogenesis.

Research Products

• [Journal Article] A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex (2014)
  • Author(s): Song J, Tamura Y, Yoshihisa T, Endo T
  • Journal Title: EMBO Rep. Volume: (in press) Pages: 670-677
  • DOI: 10.1002/embr.201338142
  • Peer Reviewed / Open Access
• [Journal Article] Ubiquitin is phosphorylated by PINK1 to activate parkin. (2014)
  • Author(s): Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., Endo, T., Fon. E. A., Trempe, J. F., Saeki, Y., Tanaka, K., and Matsuda, N.
  • Journal Title: Nature Volume: 510(in press) Issue: 7503 Pages: 162-166
  • DOI: 10.1038/nature13392
  • Peer Reviewed
• [Journal Article] Biosynthesis and roles of phospholipids in mitochondrial fusion, division and mitophagy. (2014)
  • Author(s): Q. Zhang, Y. Tamura, M. Roy, Y. Adachi, M. Iijima, H. Sesaki
  • Journal Title: Cell Mol. Life. Sci Volume: 71 Issue: 19 Pages: 162-166
  • DOI: 10.1007/s00018-014-1648-6
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phospholipid transport via mitochondria. (2014)
  • Author(s): Tamura Y. Sesaki H. and Endo T.
  • Journal Title: Traffic Volume: 15 Issue: 9 Pages: 933-945
  • DOI: 10.1111/tra.12188
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intra-molecular disulfide bond of Tim22 maintains integrity of the TIM22 complex in the mitochondrial inner membrane. (2014)
  • Author(s): Okamoto, H., Miyagawa, A., Shiota, T., Tamura, Y. and Endo, T.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Pages: 4827-4838
  • Peer Reviewed
• [Journal Article] Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria. (2013)
  • Author(s): Tamura, Y., Harada, Y., Nishikawa, S., Yamano, K., Kamiya, M., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K. and Endo, T.
  • Journal Title: Cell Metabolism Volume: 17 Pages: 709-718
  • Peer Reviewed
• [Presentation] Structural and Mechanistic Insights into phospholipid transfer via mitochondria (2015)
  • Author(s): Tamura Y. Watanabe Y. Kawano S. Endo T.
  • Organizer: Progress 100: Kyushu-U and Stanford-U Joint Research and Education Program, First Symposium: From Genes to Human Diseases
  • Place of Presentation: Centennial Hall, Kyushu University School of Medicine
  • Year and Date: 2015-03-16 – 2015-03-17
  • Invited
• [Presentation] Phospholipid trafficking between mitochondria and the endoplasmic reticulum (2014)
  • Author(s): Tamura Y. Watanabe Y. Kawano S. Endo T.
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] 試験管内リン脂質輸送反応アッセイ系の開発 (2014)
  • Author(s): 田村康，遠藤斗志也
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良県新公会堂
  • Year and Date: 2014-06-11 – 2014-06-13
  • Invited
• [Presentation] ミトコンドリア型CDP-DAG合成酵素の発見 (2013)
  • Author(s): 田村康, 遠藤斗志也
  • Organizer: 第65回日本細胞生物学会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] ミトコンドリアにおけるリン脂質生合成経路 (2013)
  • Author(s): 田村康，谷口真由美，神谷恵，遠藤斗志也
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Tam41 is a CDP-diacylglycerol synthase for cardiolipin biosynthesis in mitochondria (2013)
  • Author(s): Tamura, Y., Harada, Y., Nishikawa, Yamano, K. Kamiya, M., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K. and Endo T.
  • Organizer: The 4th International Symposium on Dynamics of Mitochondria - from Molecular Mechanisms to Physiological Functions and Disease
  • Place of Presentation: 沖縄
• [Presentation] ミトコンドリアリン脂質組成維持に関わる因子の機能解析 (2013)
  • Author(s): 田村康，谷口真由美，神谷恵，遠藤斗志也
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Remarks] Tam41はミトコンドリアにおけるカルジオリピンの合成に必要なCDP-DAG合成酵素である
  • URL: http://first.lifesciencedb.jp/archives/7035
• [Remarks] 人の健康に大切なミトコンドリア:その機能を支える脂質の作り方
  • URL: http://www.aip.nagoya-u.ac.jp/extramural/nu_research_ja/highlights/detail/0000804.html
• [Remarks] ミトコンドリア機能に必須の脂質「カルジオリピン」合成の鍵を握る酵素の発見
  • URL: http://biochem.chem.nagoya-u.ac.jp/index.html