Regulatory mechanism of delipidation of Atg8 that mediates autophagosome formation

• Project/Area Number: 26870828
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology; Physical pharmacy
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: FUJIOKA Yuko (NODA Yuko) 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 (80399964)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: オートファジー / X線結晶構造解析

Outline of Final Research Achievements

Atg8, a ubiquitin-like protein important for membrane dynamics　during　autophagy,　is　modified　with　a　phospholipid　and　localizes　to　the　membrane,　thereby　contributes to the progression of autophagy. Atg4 is a deconjugating enzyme for lapidated Atg8 and contributes to the recycling of Atg8; however, the regulation mechanism of Atg4 activity remained elusive. Here, I studied the components that regulate Atg4 activity in vitro. The data showed that the activity of Atg4 was affected by neither the interaction with other Atg proteins nor Atg1-mediated phosphorylation, but by the regulatory regions within Atg4. These data suggested that Atg4 might possess an ability to regulate its deconjugating activity depending on the intracellular localization.

Research Products

• [Journal Article] Structural biology of the core autophagy machinery. (2017)
  • Author(s): Suzuki H, Osawa T, Fujioka Y, Noda NN
  • Journal Title: Current Opinion in Structural Biology Volume: 43 Pages: 10-17
  • DOI: 10.1016/j.sbi.2016.09.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes. (2016)
  • Author(s): Yamamoto H, Fujioka Y, Suzuki SW, Noshiro D, Suzuki H, Kondo-Kakuta C, Kimura Y, Hirano H, Ando T, Noda NN, Ohsumi Y
  • Journal Title: Developmental Cell Volume: 38 Issue: 1 Pages: 86-99
  • DOI: 10.1016/j.devcel.2016.06.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Structural basis of the differential function of the two C. elegans Atg8 homologs, LGG-1 and LGG-2, in autophagy. (2015)
  • Author(s): Wu, F., Watanabe, Y., Guo, X. Y., Qi, X., Wang, P., Zhao, H. Y., Wang, Z., Fujioka, Y., Zhang, H., Ren, J. Q., Fang, T. C., Shen, Y. X., Feng, W., Hu, J. J., Noda, N. N., Zhang, H.
  • Journal Title: Molecular Cell Volume: 60 Issue: 6 Pages: 914-929
  • DOI: 10.1016/j.molcel.2015.11.019
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Atg1 family kinases in autophagy initiation. (2015)
  • Author(s): Noda, N. N., Fujioka, Y.
  • Journal Title: Cellular and Molecular Life Sciences Volume: 72 Issue: 16 Pages: 3083-3096
  • DOI: 10.1007/s00018-015-1917-z
  • Peer Reviewed / Open Access
• [Journal Article] Structural Basis of Starvation-induced Assembly of the Autophagy Initiation Complex (2015)
  • Author(s): 藤岡優子、野田展生
  • Journal Title: Nihon Kessho Gakkaishi Volume: 57 Issue: 3 Pages: 191-197
  • DOI: 10.5940/jcrsj.57.191
  • NAID: 130005085906
  • ISSN: 0369-4585, 1884-5576
  • Peer Reviewed / Open Access
• [Journal Article] Structural basis of starvation-induced assembly of the autophagy initiation complex (2014)
  • Author(s): Yuko Fujioka, Sho W Suzuki, Hayashi Yamamoto, Chika Kondo-Kakuta, Yayoi Kimura, Hisashi Hirano, Rinji Akada, Fuyuhiko Inagaki, Yoshinori Ohsumi, Nobuo N Noda
  • Journal Title: NATURE STRUCTURAL & MOLECUIAR BIOLOGY Volume: 21(発表確定) Issue: 6 Pages: 513-521
  • DOI: 10.1038/nsmb.2822
  • Peer Reviewed
• [Presentation] Structural basis of the pre-autophagosomal structure assembly mediated by an intrinsically disordered protein Atg13 (2016)
  • Author(s): 藤岡優子,山本林,鈴木翔,大隅良典,野田展生
  • Organizer: 内藤コンファレンス「生命科学に革命をもたらす最先端構造生物学」
  • Place of Presentation: シャトレーゼガトーキングダムサッポロ（北海道 札幌市）
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] プレオートファゴソーム構造体の中核複合体のin vitro再構成と性状解析 (2015)
  • Author(s): 藤岡優子, 山本 林, 鈴木 翔, 大隅良典, 野田展生
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県 神戸市）
  • Year and Date: 2015-12-01
• [Presentation] PASの中核複合体のin vitro再構成と溶液構造解析 (2015)
  • Author(s): 藤岡優子, 山本 林, 鈴木 翔, 能代大輔，有坂文雄, 安藤敏夫，大隅良典, 野田展生
  • Organizer: 第9回オートファジー研究会
  • Place of Presentation: 淡路夢舞台（兵庫県 淡路市）
  • Year and Date: 2015-11-16
• [Presentation] Molecular mechanism of PAS (pre-autophagosomal structure) organization. (2014)
  • Author(s): Fujioka Y, Suzuki SW, Yamamoto H, Kondo-Kakuta C, Kimura Y, Hirano H, Akada R, Inagaki F, Ohsumi Y, Noda NN.
  • 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
  • Invited
• [Remarks] 微生物化学研究所HP
  • URL: http://www.bikaken.or.jp/
• [Remarks] 微生物化学研究所 HP
  • URL: http://www.bikaken.or.jp/