Elucidation of the mechanism of lipidation of a ubiquitin-like protein that drives autophagosome formation

• Project/Area Number: 26840017
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Nakatogawa Machiko 東京工業大学, 生命理工学院, JSPS特別研究員 (90402461)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オートファジー / ユビキチン様タンパク質 / E2酵素 / 蛍光顕微鏡 / 結晶構造解析 / E3酵素

Outline of Final Research Achievements

Autophagy is a lysosome/vacuole-mediated degradation system in eukaryotic cells, involved in various diseases such as neurodegenerative diseases, hepatic diseases, cancer, and diabetes. Formation of double-membrane vesicles “autophagosomes” that enwrap degradation targets is essential for autophagy. In this study, we revealed the localization of the autophagy-related protein Atg3 to autophagosome intermediates under autophagy-inducing conditions, and that the impairment of its localization results in inefficient autophagosome formation. Based on our results, we proposed the mechanism by which Atg3 participate in autophagosome formation.

Research Products

• [Journal Article] Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling (2015)
  • Author(s): Sakakibara K, Eiyama A, Suzuki SW, Sakoh-Nakatogawa M, Okumura N, Tani M, Hashimoto A, Nagumo S, Kondo-Okamoto N, Kondo-Kakuta C, Asai E, Kirisako H, Nakatogawa H, Kuge O, Takao T, Ohsumi Y, Okamoto K
  • Journal Title: EMBO Journal Volume: 34 Issue: 21 Pages: 2703-2719
  • DOI: 10.15252/embj.201591440
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Localization of Atg3 to autophagy-related membranes and its enhancement by the Atg8-family interacting motif to promote expansion of the membranes (2015)
  • Author(s): Sakoh-Nakatogawa M, Kirisako H, Nakatogawa H*, Ohsumi Y*
  • Journal Title: FEBS Lett. Volume: 589 Issue: 6 Pages: 744-749
  • DOI: 10.1016/j.febslet.2015.02.003
  • Peer Reviewed
• [Journal Article] A novel role for 12/15-lipoxygenase in regulating autophagy. (2015)
  • Author(s): Alwena H. Morgan, Victoria J. Hammond, Machiko Sakoh-Nakatogawa, Yoshinori Ohsumi, Christopher P. Thomas, Fabien Blanchet, Vincent Piguet, Kirill Kiselyov, Valerie B. O’Donnell
  • Journal Title: Redox Biology Volume: 4 Pages: 40-47
  • DOI: 10.1016/j.redox.2014.11.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hrr25 triggers selective autophagy-related pathways by phosphorylating receptor proteins (2014)
  • Author(s): Tanaka C, Tan LJ, Mochida K, Kirisako H, Koizumi M, Asai E, Sakoh-Nakatogawa M, Ohsumi Y, Nakatogawa H.
  • Journal Title: J. Cell Biol Volume: 207 Issue: 1 Pages: 91-105
  • DOI: 10.1083/jcb.201402128
  • Peer Reviewed
• [Presentation] オートファゴソーム形成を駆動するユビキチン様タンパク質脂質化反応のメカニズム (2014)
  • Author(s): 中戸川万智子、的場一晃、野田展生、稲垣冬彦、中戸川仁、大隅良典
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜/横浜産貿ホール マリネリア（横浜）
  • Year and Date: 2014-06-25 – 2014-06-27
  • Invited
• [Presentation] Regulation of lipidation of the ubiquitin-like protein Atg8 that drives autophagosome formation (2014)
  • Author(s): Machiko Sakoh-Nakatogawa, Kazuaki Matoba, Nobuo Noda, Fuyuhiko Inagaki, Hitoshi Nakatogawa, Yoshinori Ohsumi
  • Organizer: The 4th Asia Pacific Protein Association Conference 2014
  • Place of Presentation: The 4th Asia Pacific Protein Association Conference 2014 (Jeju, Korea)
  • Year and Date: 2014-05-17 – 2014-05-20
  • Invited
• [Remarks] Atg3はAIMを介してPAS及び隔離膜に蓄積し膜の伸張を促進する
  • URL: http://proteolysis.jp/a_forum/thread.php?id=56
• [Remarks] 出芽酵母における Hrr25 による選択的オートファジーの制御機構
  • URL: http://proteolysis.jp/a_forum/thread.php?id=50