Structural biology studies of autophagy-related protein Atg9

• Project/Area Number: 18K06097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: Matoba Kazuaki 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (60613792)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オートファジー / クライオ電子顕微鏡 / クライオ 電子顕微鏡 / Atg9

Outline of Final Research Achievements

During this study, we showed that the recombinant Atg9 had lipid scrambling activity in vitro. Atg9 structure was then determined by single particle analysis using cryo-EM (3.0Å resolution). Based on the structure, mutants were prepared, and mutants with reduced lipid scrambling activity were found. These mutants were not able to elongate isolation membranes in yeast. This suggests that the lipid scrambling activity of Atg9 is necessary for the normal progression of autophagy.

Academic Significance and Societal Importance of the Research Achievements

オートファジーが機能する上で必須のタンパク質であるAtg9の機能と立体構造を明らかにし、オートファジーの特徴である隔離膜がどのように伸びるのか、膜伸展モデルを提唱することができた。これらの作動原理は学術的にインパクトがあるだけでなく、Atg9の構造をもとにしたオートファジー制御剤の開発に貢献できる。

Research Products

• [Journal Article] Structural catalog of core Atg proteins opens new era of autophagy research (2021)
  • Author(s): Matoba Kazuaki、Noda Nobuo N
  • Journal Title: The Journal of Biochemistry Volume: － Issue: 5 Pages: 1-9
  • DOI: 10.1093/jb/mvab017
  • Peer Reviewed / Open Access
• [Journal Article] Secret of Atg9: lipid scramblase activity drives de novo autophagosome biogenesis (2020)
  • Author(s): Matoba Kazuaki、Noda Nobuo N.
  • Journal Title: Cell Death & Differentiation Volume: 27 Issue: 12 Pages: 3386-3388
  • DOI: 10.1038/s41418-020-00663-1
  • Peer Reviewed
• [Journal Article] Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion (2020)
  • Author(s): Matoba Kazuaki、Kotani Tetsuya、Tsutsumi Akihisa、Tsuji Takuma、Mori Takaharu、Noshiro Daisuke、Sugita Yuji、Nomura Norimichi、Iwata So、Ohsumi Yoshinori、Fujimoto Toyoshi、Nakatogawa Hitoshi、Kikkawa Masahide、Noda Nobuo N.
  • Journal Title: Nature Structural & Molecular Biology Volume: 27 Issue: 12 Pages: 1185-1193
  • DOI: 10.1038/s41594-020-00518-w
  • Peer Reviewed / Open Access
• [Journal Article] Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes (2020)
  • Author(s): Mochida Keisuke、Yamasaki Akinori、Matoba Kazuaki、Kirisako Hiromi、Noda Nobuo N.、Nakatogawa Hitoshi
  • Journal Title: Nature Communications Volume: 11, 3306 Issue: 1 Pages: 3306-3306
  • DOI: 10.1038/s41467-020-17163-y
  • Peer Reviewed / Open Access
• [Remarks] 微生物化学研究所
  • URL: https://www.bikaken.or.jp/