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Proteins escape from autophagic degradation

Research Project

Project/Area Number 19K22419
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
Research InstitutionNiigata University

Principal Investigator

KANKI TOMOTAKE  新潟大学, 医歯学系, 教授 (50398088)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsオートファジー / オルガネラ / タンパク質分解 / 基質
Outline of Research at the Start

オートファジーは、細胞質のタンパク質やオルガネラをオートファゴソームと呼ばれる膜構造体に包み込んだのち、内容物をリソソームあるいは液胞内に運んで分解する経路である。従来、オートファジーは、ほとんどの細胞質成分を等しく分解していると考えられており、特定の基質がオートファジーによる分解を免れているとは考えられていなかった。本研究では、特定の基質がオートファジーを免れる機構が存在すると推測し、その解明を行う。

Outline of Final Research Achievements

Autophagy is a process that degrades proteins and organelles by transporting them into lysosomes (or vacuoles in yeast and plants). Although proteins are thought to be degraded randomly, it is conceivable that some of them are selectively escape from the degradation. In this study, we tested whether there are cellular components that are escape from autophagic degradation.
Using budding yeast and fission yeast, we tagged GFP on the C-terminus of various proteins and observed their degradation. Although most of cytosolic proteins were equally degraded, we found that proteins localized to the organelle were degraded more slowly than most of cytosolic proteins, even if they were localized on the cytoplasmic side at the organelle surface.

Academic Significance and Societal Importance of the Research Achievements

オートファジーは細胞質成分を無作為に分解する現象であると考えられていたが、最近の研究から、一部のタンパク質複合体やオルガネラが、選択的に分解されていることが明らかになった。オートファジーは様々なストレスに応答して誘導される現象であり、そのストレスに耐性をもたらす因子を分解することは非合理的である。このため、こうした因子は、オートファジーによる分解を免れている可能性がある。本研究では、こうした因子の同定を試みたが、タンパク質ごとに分解程度に差があることは見いだせたものの、分解が強く抑制されている因子は同定できなかった。本研究が布石となり、今後解明が進んでいくことが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (2 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] Mitophagy in Yeast: Molecular Mechanism and Regulation2021

    • Author(s)
      Innokentev Aleksei、Kanki Tomotake
    • Journal Title

      Cells

      Volume: 10 Issue: 12 Pages: 3569-3569

    • DOI

      10.3390/cells10123569

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitophagy regulation mediated by the Far complex in yeast2021

    • Author(s)
      Furukawa Kentaro、Innokentev Aleksei、Kanki Tomotake
    • Journal Title

      Autophagy

      Volume: 17 Issue: 4 Pages: 1042-1043

    • DOI

      10.1080/15548627.2021.1885184

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atg43, a novel autophagy-related protein, serves as a mitophagy receptor to bridge mitochondria with phagophores in fission yeast2021

    • Author(s)
      Fukuda Tomoyuki、Kanki Tomotake
    • Journal Title

      Autophagy

      Volume: 17 Issue: 3 Pages: 826-827

    • DOI

      10.1080/15548627.2021.1874662

    • Related Report
      2020 Research-status Report
  • [Journal Article] MITOL promotes cell survival by degrading Parkin during mitophagy2021

    • Author(s)
      Shiiba Isshin、Takeda Keisuke、Nagashima Shun、Ito Naoki、Tokuyama Takeshi、Yamashita Shun‐Ichi、Kanki Tomotake、Komatsu Toru、Urano Yasuteru、Fujikawa Yuuta、Inatome Ryoko、Yanagi Shigeru
    • Journal Title

      EMBO reports

      Volume: 22 Issue: 3

    • DOI

      10.15252/embr.201949097

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase2021

    • Author(s)
      Fukuda Tomoyuki、Sofyantoro Fajar、Tai Yen Teng、Chia Kim Hou、Matsuda Takato、Murase Takaaki、Morozumi Yuichi、Tatebe Hisashi、Kanki Tomotake、Shiozaki Kazuhiro
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.60969

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy2020

    • Author(s)
      Innokentev Aleksei、Furukawa Kentaro、Fukuda Tomoyuki、Saigusa Tetsu、Inoue Keiichi、Yamashita Shun-ichi、Kanki Tomotake
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.63694

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast2020

    • Author(s)
      Fukuda Tomoyuki、Ebi Yuki、Saigusa Tetsu、Furukawa Kentaro、Yamashita Shun-ichi、Inoue Keiichi、Kobayashi Daiki、Yoshida Yutaka、Kanki Tomotake
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.61245

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gemcitabine induces Parkin-independent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1.2020

    • Author(s)
      Igarashi R, Yamashita SI, Yamashita T, Inoue K, Fukuda T, Fukuchi T, Kanki T.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 1465-1465

    • DOI

      10.1038/s41598-020-58315-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FKBP8 LIRL‐dependent mitochondrial fragmentation facilitates mitophagy under stress conditions2020

    • Author(s)
      Yoo Seung‐Min、Yamashita Shun‐ichi、Kim Hyunjoo、Na DoHyeong、Lee Haneul、Kim Seo Jin、Cho Dong‐Hyung、Kanki Tomotake、Jung Yong‐Keun
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 2 Pages: 2944-2957

    • DOI

      10.1096/fj.201901735r

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory mechanisms of mitochondrial autophagy: Lessons from yeast2019

    • Author(s)
      Kentaro Furukawa, Aleksei Innokentev, Tomotake Kanki
    • Journal Title

      Frontiers in Plant Science

      Volume: 10 Pages: 1479-1479

    • DOI

      10.3389/fpls.2019.01479

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ミトコンドリアオートファジーの誘導機構2021

    • Author(s)
      神吉智丈
    • Organizer
      J-mit 特別 オンラインシンポジウム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアオートファジーの分子機構2021

    • Author(s)
      神吉智丈
    • Organizer
      第23回植物オルガネラワークショップ
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] 新潟大学大学院医歯学総合研究科機能制御学分野

    • URL

      https://www.med.niigata-u.ac.jp/mit/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 新潟大学大学院医歯学総合研究科 機能制御学分野

    • URL

      https://www.med.niigata-u.ac.jp/mit/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-07-04   Modified: 2023-01-30  

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