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Elucidation of novel physiological functions of autophagy-related factors using zebrafish

Research Project

Project/Area Number 18K14694
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44010:Cell biology-related
Research InstitutionJuntendo University (2019)
The University of Tokyo (2018)

Principal Investigator

Morishita Hideaki  順天堂大学, 医学部, 講師 (90783499)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー関連因子 / ゼブラフィッシュ / 水晶体 / 大規模オルガネラ分解 / ラメラ体 / リソソーム関連オルガネラ / 小胞体 / リポタンパク質 / オートファジー / リソソーム / オルガネラ分解 / 浮袋
Outline of Final Research Achievements

Autophagy is governed by various autophagy-related (ATG) proteins, but their physiological functions in vertebrates have not been fully understood. Here, using zebrafish and mice as model organisms, we revealed novel autophagy-dependent and/or -independent functions of ATG factors in several tissues including the intestine, liver, and lung. We further identified a cytosolic lipase-mediated mechanism of organelle degradation in the lens that do not require any ATG factors. These findings demonstrate critical roles of ATG factors in vivo as well as a novel autophagy-independent mechanism of organelle degradation.

Academic Significance and Societal Importance of the Research Achievements

本研究の3つの成果は以下の理由でヒト疾患の病態解明、治療につながることが期待される。第一にVMP1のリポタンパク質分泌における新たな機能は、これまでに十分に明らかにされていなかったリポタンパク質の分泌機構の一端を解明したものであり、脂質異常症等の血中リポタンパク質の量の異常を伴うヒト疾患の新たな治療標的となりうる。第二に今回解明した肺のサーファクタント形成におけるオートファジーの役割は、新生児呼吸逼迫症候群等の肺拡張不全を伴うヒト疾患の病態の理解につながる。第三に今回解明した水晶体の透明性・屈折率の獲得に関する知見は、ヒト白内障等の病態の理解や新たな治療戦略につながる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Journal Article] オートファジー関連因子の非オートファジー機能2020

    • Author(s)
      森下 英晃
    • Journal Title

      医学のあゆみ

      Volume: 272 Pages: 737-744

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Diverse Cellular Roles of Autophagy2019

    • Author(s)
      Morishita Hideaki、Mizushima Noboru
    • Journal Title

      Annual Review of Cell and Developmental Biology

      Volume: 35 Issue: 1 Pages: 453-475

    • DOI

      10.1146/annurev-cellbio-100818-125300

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A critical role of VMP1 in lipoprotein secretion2019

    • Author(s)
      Morishita Hideaki、Zhao Yan G、Tamura Norito、Nishimura Taki、Kanda Yuki、Sakamaki Yuriko、Okazaki Mitsuyo、Li Dongfang、Mizushima Noboru
    • Journal Title

      eLife

      Volume: 8 Pages: 1-24

    • DOI

      10.7554/elife.48834

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation2018

    • Author(s)
      Morita Keigo、Hama Yutaro、Izume Tamaki、Tamura Norito、Ueno Toshihide、Yamashita Yoshihiro、Sakamaki Yuriko、Mimura Kaito、Morishita Hideaki、Shihoya Wataru、Nureki Osamu、Mano Hiroyuki、Mizushima Noboru
    • Journal Title

      The Journal of Cell Biology

      Volume: 217 Issue: 11 Pages: 3817-3828

    • DOI

      10.1083/jcb.201804132

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] A cytosolic phospholipase-mediated organellar degradation in the lens2019

    • Author(s)
      Hideaki Morishita, Tomoya Eguchi, Noboru Mizushima
    • Organizer
      International Conference on the Lens 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel macroautophagy-independent mechanism of organelle degradation in the lens2019

    • Author(s)
      Hideaki Morishita, Tomoya Eguchi, Satoshi Tsukamoto, Noboru Mizushima
    • Organizer
      The 9th International Symposium on Autophagy
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 水晶体における新規オルガネラ膜分解機構の同定と生理的意義の解明2019

    • Author(s)
      森下英晃、江口智也、塚本智史、水島昇
    • Organizer
      第12回オートファジー研究会・第1回新学術領域研究「マルチモードオートファジー」班会議
    • Related Report
      2019 Annual Research Report
  • [Presentation] 水晶体における新規膜系オルガネラ分解機構の解明2019

    • Author(s)
      森下英晃、江口智也、塚本智史、水島昇
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Live imaging and molecular dissection of organelle degradation in the lens2019

    • Author(s)
      Hideaki Morishita, Tomoya Eguchi, Satoshi Tsukamoto, Noboru Mizushima
    • Organizer
      EMBO Workshop (Autophagy: From molecular principles to human diseases)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 水晶体オルガネラ分解の分子機構と生理的意義の解明2019

    • Author(s)
      森下英晃、江口智也、塚本智史、水島昇
    • Organizer
      第58回日本白内障学会総会/第45回水晶体研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脊椎動物におけるオートファジー関連遺伝子群の新たな生理機能2019

    • Author(s)
      森下英晃、神田侑季、千野 遥、酒巻有里子、貝塚剛志、水島昇
    • Organizer
      第66回 日本実験動物学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 脊椎動物におけるオートファジー関連因子群の新たな生理機能2019

    • Author(s)
      森下英晃、田村律人、神田侑季、酒巻有里子、水島昇
    • Organizer
      第19回 東京大学生命科学シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] オートファジー関連因子WDR45/WDR45Bの脳神経系細胞における機能解析2019

    • Author(s)
      森下英晃、神田侑季,田村律人,水島昇
    • Organizer
      新学術領域研究「脳タンパク質老化と認知症制御」第9回班員会議
    • Related Report
      2018 Research-status Report
  • [Presentation] Autophagy is required for formation of surfactant-containing lamellar bodies in alveolar and swimbladder epithelial cells2019

    • Author(s)
      Hideaki Morishita, Yuki Kanda, Haruka Chino, Takeshi Kaizuka, Yuriko Sakamaki, Noboru Mizushima
    • Organizer
      Keystone Sumposia Autophagy: FromModel Systems to Therapeutic Opportunities
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] オートファジーの分子メカニズムと疾患モデル動物開発2018

    • Author(s)
      森下英晃
    • Organizer
      第60回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] オートファジーの生理機能とヒト遺伝性疾患との関連2018

    • Author(s)
      森下英晃
    • Organizer
      第12回生態影響試験実習セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] オートファジー関連因子WDR45に変異を伴う脳神経変性疾患SENDAの病態解明2018

    • Author(s)
      森下英晃,神田侑季,田村律人,清水宏,村松一洋,柿田明美,水島昇
    • Organizer
      新学術領域研究「脳タンパク質老化と認知症制御」第8回班員会議
    • Related Report
      2018 Research-status Report
  • [Presentation] 水晶体細胞の最終分化過程におけるオルガネラ分解機構の解明2018

    • Author(s)
      森下英晃、江口智也、水島昇
    • Organizer
      第57 回日本白内障学会総会/第44 回水晶体研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脊椎動物におけるオートファジー関連因子群の新たな生理機能2018

    • Author(s)
      森下英晃、田村律人、神田侑季、千野遥、江口智也、西村多喜、酒巻有里子、貝塚剛志、岡崎三代、山本林、水島昇
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 小胞体膜タンパク質VMP1はリポタンパク質の小胞体からの脱離に必要である2018

    • Author(s)
      森下英晃、田村律人、Yan GZhao、西村多喜、神田侑季、酒巻有里子、岡崎三代、Dongfang Li、Hong Zhang、水島昇
    • Organizer
      第11回オートファジー研究会
    • Related Report
      2018 Research-status Report
  • [Book] 決定版 阻害剤・活性化剤ハンドブック2019

    • Author(s)
      濱 祐太郎, 森下英晃, 水島 昇
    • Publisher
      羊土社
    • ISBN
      9784758120999
    • Related Report
      2019 Annual Research Report
  • [Remarks] リポタンパク質の分泌の仕組みの解明に新たな手がかり―小胞体膜タンパク質 VMP1 の新規機能を発見―

    • URL

      https://www.m.u-tokyo.ac.jp/news/admin/release_20190917.pdf

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2021-02-19  

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