2013 Fiscal Year Final Research Report
Mechanical control of energy metabolism in cardiomyocytes
Project/Area Number |
24657127
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Single-year Grants |
Research Field |
Cell biology
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2014-03-31
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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.
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Research Products
(9 results)
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[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
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Journal Title
The American Journal of Human Genetics
Volume: 93
Pages: 173-180
Peer Reviewed
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[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.
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Journal Title
Nature Communications
Volume: 4
Pages: Article number 1978
DOI
Peer Reviewed
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