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Intracellular signaling network that controls lifespan in response to nutrient availability.

Research Project

Project/Area Number 19H03224
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Shiozaki Kazuhiro  奈良先端科学技術大学院大学, 事務局, 学長 (00610015)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsmTORC1 / 栄養 / 分裂酵母 / リン酸化 / 栄養環境 / mTOR / 継時寿命
Outline of Research at the Start

わが国を含む先進国の多くで高齢化が進む中、寿命を左右する要因に対する関心はこれまでになく高い。栄養の摂取制限に寿命延長効果があることは、多様な生物種で報告されているが、栄養に応答して代謝を制御するタンパク質キナーゼ mTORが、寿命をコントロールする主要な細胞内因子の1つであると考えられている。本研究では、遺伝学的解析の容易な分裂酵母をモデル系として、栄養源に応答したmTOR活性制御機構を明らかにするとともに、その寿命決定における役割を解明する。

Outline of Final Research Achievements

Limited nutrient uptake extends lifespan in diverse organisms. The mechanistic Target Of Rapamycin (mTOR), a nutrient-responsive protein kinase that controls cellular metabolism, is believed to be one of the major regulators of longevity. Using fission yeast as a model system, we have demonstrated that mTOR regulates chronological lifespan through the transcriptional regulator Maf1. Our study has also identified novel mechanisms that control the activity substrate recognition of mTORC1.

Academic Significance and Societal Importance of the Research Achievements

わが国を含む先進国の多くで高齢化が進む中、寿命を左右する要因に対する関心はこれまでになく高い。食餌制限に寿命延長効果があることは、酵母から哺乳類に至る多様な生物種で報告されており、本研究では遺伝学的操作の容易な分裂酵母をモデルとして、栄養に応答する細胞内因子 mTORC1が寿命を制御する分子メカニズムの一端を明らかにした。本研究で得られた知見を基盤に、ヒトを含む高等生物における栄養と寿命の関係の理解が進むものと期待される。

Report

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

    (23 results)

All 2021 2019 Other

All Int'l Joint Research (8 results) Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] Universitas Gadjah Mada(インドネシア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California, Davis(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Drexel University/University of California, Davis(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Universitas Gadjah Mada(インドネシア)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Drexel University/University of California, Davis(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Universitas Gadjah Mada(インドネシア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The University of Namur(ベルギー)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Edinburgh/University of Warwick(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Fission yeast TOR complex 1 phosphorylates Psk1 through an evolutionarily conserved interaction mediated by the TOS motif2021

    • Author(s)
      Morozumi Yuichi、Hishinuma Ai、Furusawa Suguru、Sofyantoro Fajar、Tatebe Hisashi、Shiozaki Kazuhiro
    • Journal Title

      Journal of Cell Science

      Volume: 134 Issue: 19 Pages: 1-9

    • DOI

      10.1242/jcs.258865

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiplexed suppression of TOR complex 1 induces autophagy during starvation2021

    • Author(s)
      Fukuda Tomoyuki、Shiozaki Kazuhiro
    • Journal Title

      Autophagy

      Volume: 17 Issue: 7 Pages: 1794-1795

    • DOI

      10.1080/15548627.2021.1938915

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals2021

    • Author(s)
      Morozumi Yuichi、Shiozaki Kazuhiro
    • Journal Title

      Genes

      Volume: 12 Issue: 1 Pages: 88-88

    • DOI

      10.3390/genes12010088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Maf1‐dependent transcriptional regulation of tRNAs prevents genomic instability and is associated with extended lifespan2019

    • Author(s)
      Shetty Mihir、Noguchi Chiaki、Wilson Sydney、Martinez Esteban、Shiozaki Kazuhiro、Sell Christian、Mell Joshua Chang、Noguchi Eishi
    • Journal Title

      Aging Cell

      Volume: 19 Issue: 2

    • DOI

      10.1111/acel.13068

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast2019

    • Author(s)
      Morigasaki Susumu、Chin Lit Chein、Hatano Tomoyuki、Emori Midori、Iwamoto Mika、Tatebe Hisashi、Shiozaki Kazuhiro
    • Journal Title

      Journal of Cell Science

      Volume: 132 Issue: 19

    • DOI

      10.1242/jcs.236133

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate2019

    • Author(s)
      Candiracci Julie、Migeot Valerie、Chionh Yok-Hian、Bauer Fanelie、Brochier Thomas、Russell Brandon、Shiozaki Kazuhiro、Dedon Peter、Hermand Damien
    • Journal Title

      Science Advances

      Volume: 5 Issue: 6

    • DOI

      10.1126/sciadv.aav0184

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] mip1変異株を用いた分裂酵母TORC1シグナル経路の新規関連因子の探索2021

    • Author(s)
      木原諒也、両角佑一、高木博史、塩﨑一裕
    • Organizer
      酵母遺伝学フォーラム 第54回研究報告会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分裂酵母TORC1構成因子Mip1による基質認識機構の解析2019

    • Author(s)
      両角佑一、建部恒、塩崎一裕
    • Organizer
      第9回TOR研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of the interaction interface between TOR complex 2 and its substrate by in-vitro and in-vivo crosslinking2019

    • Author(s)
      Hisashi Tatebe, Keita Oka, Yue Keong Choon, Kazuma Sera, Kazuhiro Shiozaki
    • Organizer
      The 10th International Fission Yeast Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 分裂酵母mTORC1によるPol III転写抑制因子Maf1のリン酸化制御2019

    • Author(s)
      伊計舞、両角佑一、塩崎一裕
    • Organizer
      酵母遺伝学フォーラム第52回研究報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of the Sin1 subunit of TOR Complex 2 (TORC2)2019

    • Author(s)
      Hisashi Tatebe, Keita Oka, Keong Choon Yue, Kazuma Sera, Kazuhiro Shiozaki
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TORC2複合体のSin1サブユニットによる基質認識機構2019

    • Author(s)
      塩崎一裕
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 分裂酵母TORC1によるRNAポリメラーゼIII抑制因子Maf1の機能制御2019

    • Author(s)
      両角佑一、伊計舞、塩崎一裕
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Remarks] 細胞シグナル研究室

    • URL

      https://bsw3.naist.jp/shiozaki/

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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