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Analysis of a molecular mechanism to improve polyglutamine diseases by activating alternative autophagy

Research Project

Project/Area Number 15K08420
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ARAKAWA Satoko  東京医科歯科大学, 難治疾患研究所, 講師 (90415159)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオートファジー / ポリグルタミン病 / ケミカルバイオロジー / ゴルジ / オルタナティブオートファジー
Outline of Final Research Achievements

Autophagy is a cellular process that degrades subcellular constituents, and is conserved from yeast to mammals. Although autophagy is believed to be essential for living cells, cells lacking Atg5 or Atg7 are healthy, suggesting that a non‐canonical degradation pathway exists to compensate for the lack of autophagy. We first showed that the budding yeast lacking Atg5 undergoes bulk protein degradation using Golgi‐mediated structures to compensate for autophagy when treated with amphotericin B1 a polyene antifungal drug. We next identified Aag4 as a molecule essential for alternative autophagy, we clarified the mechanism of alternative autophagy and its physiological roles. Finally, we discovered several chemicals to induce alternative autophagy but not conventional autophagy. One of them reduced the polyglutamine aggregation in the cytosol, which causes polyglutamine diseases. We are currently observing the process of the aggregation formation and the drug effects on it using EM.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Dram1 regulates DNA damage-induced alternative autophagy2018

    • Author(s)
      Nagata M, Arakawa S, Yamaguchi H, Torii S, Endo H, Tsujioka M, Honda S, Nishida Y, Konishi A, Shimizu S
    • Journal Title

      Cell Stress

      Volume: 2 Issue: 3 Pages: 55-65

    • DOI

      10.15698/cst2018.03.127

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function2018

    • Author(s)
      Yamaguchi Tomokazu et al
    • Journal Title

      Science Signaling

      Volume: 11 Issue: 516 Pages: 3638-3638

    • DOI

      10.1126/scisignal.aan3638

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular trap formation2017

    • Author(s)
      Yotsumoto Satoshi、Muroi Yuito、Chiba Tatsuya、Ohmura Rio、Yoneyama Maki、Magarisawa Megumi、Dodo Kosuke、Terayama Naoki、Sodeoka Mikiko、Aoyagi Ryohei、Arita Makoto、Arakawa Satoko、Shimizu Shigeomi、Tanaka Masato
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16026-16026

    • DOI

      10.1038/s41598-017-15668-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Atg5-dependent cell death in the embryonic development of Bax/Bak double-knockout mice2017

    • Author(s)
      Arakawa S, Tsujioka M, Yoshida T, Tajima-Sakurai H, Nishida Y, Matsuoka Y, Yoshino I, Tsujimoto Y, Shimizu S.
    • Journal Title

      Cell death and differ

      Volume: 9 Issue: 9 Pages: 1598-1608

    • DOI

      10.1038/cdd.2017.84

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Golgi membrane-associated degradation pathway in yeast and mammals2016

    • Author(s)
      H. Yamaguchi, S. Arakawa, T. Kanaseki, T. Miyatsuka, Y. Fujitani, H. Watada, Y. Tsujimoto, S. Shimizu
    • Journal Title

      EMBO J.

      Volume: 35 Issue: 18 Pages: 1991-2007

    • DOI

      10.15252/embj.201593191

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autophagy controls centrosome number by degrading Cep63.2016

    • Author(s)
      Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 13508-13508

    • DOI

      10.1038/ncomms13508

    • NAID

      120007129257

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress‐induced autophagy2016

    • Author(s)
      S. Torii, T. Yoshida, S. Arakawa, S. Honda, A. Nakanishi, S. Shimizu
    • Journal Title

      EMBO reports

      Volume: 11 Issue: 11 Pages: 1552-1564

    • DOI

      10.15252/embr.201642565

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] In Situ Characterization of Bak Clusters Responsible for Cell Death Using Single Molecule Localization Microscopy2016

    • Author(s)
      Y. Nasu, A. Benke, S. Arakawa, G. Yoshida, G. Kawamura, S. Manley, S. Shimizu, T. Ozawa
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 27505-27505

    • DOI

      10.1038/srep27505

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis.2015

    • Author(s)
      Arakawa S, Nakanomyo I, Kudo-Sakamoto Y, Akazawa H, Komuro I, Shimizu S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 467 Pages: 1006-1011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] ゴルジ体を介したタンパク質分解システムの発見2017

    • Author(s)
      荒川聡子、山口啓史、清水重臣
    • Organizer
      生命科学系学会合同年次大会(ConBio2017)(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] オートファジー細胞死の個体での解析2017

    • Author(s)
      荒川聡子、清水重臣
    • Organizer
      新学術ダイイングコード 細胞死を起点とする生体制御ネットワークの解明〜
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゴルジ体を介したタンパク質分解システムの発見2016

    • Author(s)
      荒川聡子、山口啓史、金関悳、清水重臣
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜、パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] ゴルジ体を介したタンパク質分解システムの発見2016

    • Author(s)
      荒川聡子
    • Organizer
      第4回新学術「オートファジー」班会議・第10回オートファジー研究会
    • Place of Presentation
      越後湯沢、NASPAニューオータニ
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
  • [Presentation] オートファジー細胞死の個体での解析2016

    • Author(s)
      荒川聡子、辻岡政経、桜井一、山口啓史、吉野育代、清水重臣
    • Organizer
      第25回日本Cell Death学会学術集会
    • Place of Presentation
      品川区、品川区立総合区民会館きゅりあん
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Induction of Atg5-independent alternative macroautophagy by a disturbance of insulin secretion of Pancreatic ß cell2015

    • Author(s)
      Satoko Arakawa, Hirofumi Yamaguchi, Toku Kanaseki, Hirotaka Watada, and Shigeomi Shimizu
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド、兵庫県神戸市
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規オートファジーの微細構造解析2015

    • Author(s)
      荒川聡子、金関悳、清水重臣
    • Organizer
      オートファジー研究会
    • Place of Presentation
      淡路夢舞台国際会議場、兵庫県淡路市
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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