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2013 Fiscal Year Final Research Report

Mechanical control of energy metabolism in cardiomyocytes

Research Project

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Project/Area Number 24657127
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionTohoku University

Principal Investigator

OGURA Toshihiko  東北大学, 加齢医学研究所, 教授 (60273851)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywords細胞力覚 / エネルギー代謝
Research Abstract

Beating heart maintains constant circulation by responding to hemodynamics changes, such as altering blood pressure and heart rate. To adapt to high blood pressure, for example, cardiomyocytes must produce more ATP to contract even under the high mechanical overload. To explore a functional link between mechanical stimuli and energetic compensation, we searched for factors that respond to mechanical forces, and found a transcriptional co-activator that shuttles from cytoplasm to nucleus in response to physical force. This co-activator robustly activates nuclear receptors that regulate lipid metabolism in beating cardiomyocytes. As a result, this co-activator increases ATP production by enhancing oxidative phosphorylation (OxPhos) in mitochondria. Our finding provides an essential and novel insight on the energetic adaptation mechanism, in which drug targets can be found for therapy of heart diseases, such as heart failure.

  • Research Products

    (9 results)

All 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (5 results) (of which Invited: 3 results)

  • [Journal Article] Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome2013

    • Author(s)
      Y. Aoki, T. Niihori, T. Banjo, N. Okamoto, S. Mizuno, K. Kurosawa, T. Ogata, F. Takada, M. Yano, T. Ando, T. Hoshika, C. Barnett, H. Ohashi, H. Kawame, T. Hasegawa, T. Okutani, T. Nagashima, S. Hasegawa, R. Funayama, T. Nagashima, K. Nakayama, S. Inoue, Y. Watanabe, T. Ogura, Y. Matsubara
    • Journal Title

      The American Journal of Human Genetics

      Volume: 93 Pages: 173-180

    • Peer Reviewed
  • [Journal Article] Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-212013

    • Author(s)
      T. Banjo, J. Grajcarek, D. Yoshino, H. Osada, K. Y. Miyasaka, Y. S. Kida, Y. Ueki, K. Nagayama, K. Kawakami, T. Matsumoto, M. Sato, T. Ogura.
    • Journal Title

      Nature Communications

      Volume: 4 Pages: Article number 1978

    • DOI

      10.1038/ncomms2978

    • Peer Reviewed
  • [Journal Article] Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium2012

    • Author(s)
      Y. Watanabe, S. Zaffran, A. Kuroiwa, H. Higuchi, T. Ogura, R. P. Harvey, R. G. Kelly, M. Buckingham.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Pages: 18273-18280

    • Peer Reviewed
  • [Journal Article] Roles of planar cell polarity signaling in maturation of neuronal precursor cells in the postnatal mouse olfactory bulb2012

    • Author(s)
      Y. Hirota, M. Sawada, Y. S. Kida, S. Huang, O. Yamada, M. Sakaguchi, T. Ogura, H. Okano, K. Sawamoto.
    • Journal Title

      Stem Cells

      Volume: 30 Pages: 1726-1733

    • Peer Reviewed
  • [Presentation] 生命現象を力学的に再解釈する、そして、生命現象を再構築する2014

    • Author(s)
      小椋利彦
    • Organizer
      東京工業大学生体システム専攻バイオサイエンスシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-02-18
    • Invited
  • [Presentation] 生命現象を力を視点に再解釈するために2013

    • Author(s)
      小椋利彦
    • Organizer
      生物物理学会東北支部
    • Place of Presentation
      仙台
    • Year and Date
      2013-12-13
    • Invited
  • [Presentation] 細胞は力をどのように感知し、そのように反応するか2013

    • Author(s)
      小椋利彦
    • Organizer
      日本人類遺伝学会大第8回大会特別講演
    • Place of Presentation
      仙台
    • Year and Date
      2013-11-21
    • Invited
  • [Presentation] Physical forces as a regulator of morphogenesis and homeostasis2013

    • Author(s)
      小椋利彦
    • Organizer
      第8回研究所ネットワーク国際シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2013-06-27
  • [Presentation] 生命現象を力を視点に再解釈する2012

    • Author(s)
      小椋利彦
    • Organizer
      第19回創発システムシンポジウム(創発夏の学校2013)
    • Place of Presentation
      大阪
    • Year and Date
      20120831-0902

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Published: 2015-06-25  

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