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2007 Fiscal Year Final Research Report Summary

Regulation of autophagyby the endocrine systems

Research Project

Project/Area Number 18370084
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MIZUSHIMA Noboru  Tokyo Medical and Dental University, Physiology and Cell Biology, Professor (10353434)

Project Period (FY) 2006 – 2007
KeywordsAutopahgy / Insulin / Diabetes Mellitus / Amino acid / mTOR / FIP200 / ULK
Research Abstract

The purpose of this project is to understand how autophagy is regulated, particularly by the endocrine systems. We first analyzed the involvement of mTOR, a master regulator of nutrient sensing, to reveal the autophagy regulation under physiological conditions. We found that suppression of mTOR activity correlated very well with autophagy induction following food withdrawal in mice. This result suggested that mTOR plays an important role in autophagy regulation in whole animals. Next we analyzed the role of the insulin signaling, which is upstream of mTOR, by using diabetes model mice. In the STZ-induced type 1 diabetes model, autophagy was actively induced in various organs such as the heart, muscle and liver even under fed conditions, while autophagy was suppressed in normal mice. Autophagy induction in the STZ mice was partially suppressed by insulin administration. However autophagy was further activated even in these insulin-deficient mice. Taken together these data suggest that although insulin is the major inhibitory factor of autophagy in vivo, there must be other factors that could regulate autophagy induced by starvation In addition, we identified a novel ULK1-interacting autophagy factor FIP200, which functions downstream of mTOR FIP200 is required for autophagy induced by either amino acid-starvation or growth factor-starvation Further analyses of the relationship between mTOR and the FIP200/ULK complex will reveal the precise mechanism of autophagy regulation and induction.

  • Research Products

    (34 results)

All 2008 2007 2006 Other

All Journal Article (16 results) (of which Peer Reviewed: 5 results) Presentation (17 results) Remarks (1 results)

  • [Journal Article] FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells.2008

    • Author(s)
      Hara, T
    • Journal Title

      J. Cell Biol. 181

      Pages: 497-510

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Autophagy fights disease through cellular self-digestion.2008

    • Author(s)
      Mizushima, N.
    • Journal Title

      Nature 451

      Pages: 1069-1075

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] オートファジーの生理および病態生理学的意義2008

    • Author(s)
      水島昇
    • Journal Title

      実験医学 26

      Pages: 272-276

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells2008

    • Author(s)
      Hara, T
    • Journal Title

      J. Cell Biol 181

      Pages: 497-510

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Autophagy fights disease through cellular self-digestion2008

    • Author(s)
      Mizushima, N.
    • Journal Title

      Nature 451

      Pages: 1069-1075

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Autophagy: process and function2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      Genes Dev. 21

      Pages: 2861-2873

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Protein turnover via autophagy: Implications for metabolism2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      Annu. Rev. Nutr. 27

      Pages: 19-39

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The role of mammalian autophagy in protein metabolism2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      P. JPN Acad. B-Phys. 82

      Pages: 39-46

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Autophagy : process and function2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      Genes Dev 27

      Pages: 2861-2873

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Protein turnover via autophagy : Implications for metabolism2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      Annu. Rev. Nutr 27

      Pages: 19-39

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The role of mammalian autophagy in protein metabolism2007

    • Author(s)
      Mizushima, N.
    • Journal Title

      P. JPN Acad. B-Phys 82

      Pages: 39-46

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] オートファジー2006

    • Author(s)
      水島昇
    • Journal Title

      炎症と免疫 121

      Pages: 569-571

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 発生・分化におけるオートファジーの役割2006

    • Author(s)
      久万亜紀子
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 1503-1506

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 哺乳類オートファジーの制御因子2006

    • Author(s)
      原 太一
    • Journal Title

      蛋白質核酸酵素 51

      Pages: 1484-1489

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] オートファジーの生理学:タンパク質代謝システムとしての役割2006

    • Author(s)
      水島昇
    • Journal Title

      医学のあゆみ 216

      Pages: 509-513

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Transgenic models of autophagy.2006

    • Author(s)
      Mizushima, N.
    • Journal Title

      Autophagy in Immunity and Infection, edited by Vojo Deretic. Wiley-VCH

      Pages: 55-67

    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] オートファジー関連因子FIP200の解析2007

    • Author(s)
      高村 聡人
    • Organizer
      BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 哺乳類Atg13ホモログの同定と解析2007

    • Author(s)
      細川 奈生
    • Organizer
      BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 哺乳類におけるVps34-Beclin1複合体結合タンパク質Atg14とVps38の同定2007

    • Author(s)
      板倉 英祐
    • Organizer
      BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Year and Date
      20071211-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] FIP200 is required for autophagosome formation and properfunction of ULK.2007

    • Author(s)
      Taichi Hara
    • Organizer
      The American Society of Cell Biology 47th Annual Meeting
    • Place of Presentation
      Washington
    • Year and Date
      20071201-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] FIP200 is required for autophagosome formation and proper function and proper function of ULK2007

    • Author(s)
      Taichi Hara
    • Organizer
      The American Society of Cell Biology
    • Place of Presentation
      Washington
    • Year and Date
      20071201-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] オートファジーの代謝生理学的意義2007

    • Author(s)
      水島昇
    • Organizer
      第49回日本先天代謝異常学会
    • Place of Presentation
      山形
    • Year and Date
      20071115-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of autophagy in protein metabolism and generation of an autophagy-regulatable cell line2007

    • Author(s)
      Noboru Mizushima
    • Organizer
      32nd FEBS Congress, Molecular Machines
    • Place of Presentation
      Vienna
    • Year and Date
      20070707-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of Autophagy in Protein Metabolism in Mammals.2007

    • Author(s)
      Noboru Mizushima
    • Organizer
      第66回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Regulation of autophagy by intracellular amino acids2006

    • Author(s)
      Akiko Kuma
    • Organizer
      The American Society of Cell Biology 46th Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      20061209-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Regulation of autophagy by intracellular amino acids2006

    • Author(s)
      Akiko Kuma
    • Organizer
      The American Society of Cell Biology : 46th Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      20061209-13
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Physiological role of autophagy in protein metabolism andthe mechanism regulating autophagy in mammals.2006

    • Author(s)
      Noboru Mizushima
    • Organizer
      4th International Symposium of Autophagy
    • Place of Presentation
      Mishima, Japan
    • Year and Date
      20061001-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Regulation of autophagy by intracellular amino acids2006

    • Author(s)
      Akiko Kuma
    • Organizer
      4th International Symposium of Autophagy
    • Place of Presentation
      Mishima, Japan
    • Year and Date
      20061001-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Physiological role of autophagy in protein metabolism and the mechanism regulating autophagy in mammals2006

    • Author(s)
      Noboru Muzushima
    • Organizer
      4th International Symposium of Autophagy
    • Place of Presentation
      Mishima, Japan
    • Year and Date
      20061001-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Generation of cell lines with tetracycline-regulated autophagic ability: Application to cell size studies.2006

    • Author(s)
      Nao Hosokawa
    • Organizer
      20th IUBMB Congress and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20060618-23
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Generation of cell lines with tetracycline-regulated autophagic ability : Application to cell size studies2006

    • Author(s)
      Nao Hosokawa
    • Organizer
      20th IUBMB Congress and 11th FAOBMB Congress
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20060618-23
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 細胞内品質管理におけるオートファジーの役割2006

    • Author(s)
      原太一
    • Organizer
      日本分子生物学会2006フオーラム.シンポジウム「神経変性疾患の新展開:病態解明から冶療まで」
    • Place of Presentation
      名古屋
    • Year and Date
      2006-12-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] オートファジーによる細胞内分解2006

    • Author(s)
      水島昇
    • Organizer
      第27回日本炎症・再生医学会教育講演
    • Place of Presentation
      東京
    • Year and Date
      2006-07-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tmd.ac.jp/med/phy2/phy2-J.html

URL: 

Published: 2010-02-04  

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