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The role of mitoNEET on the regulation of mitochondrial function in skeletal muscle failure

Research Project

Project/Area Number 26350879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionHokkaido University

Principal Investigator

Kinugawa Shintaro  北海道大学, 医学研究科, 講師 (60399871)

Co-Investigator(Kenkyū-buntansha) 筒井 裕之  九州大学, 医学研究院, 教授 (70264017)
松島 将士  九州大学, 大学病院, 助教 (80552869)
横田 卓  北海道大学, 医学研究科, 助教 (90374321)
Research Collaborator FURIHATA Takaaki  
TAKADA Shingo  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsミトコンドリア / 骨格筋不全 / 鉄代謝
Outline of Final Research Achievements

In various chronic disease model mice, exercise capacity was reduced, skeletal muscle abnormalities such as mitochondrial dysfunction in the skeletal muscle and fiber type switch occurred, iron content within mitochondria was increased, and oxidative stress was enhanced. In mice deleted mitoNEET, we newly created, iron content within mitochondria was increased, oxidative stress was enhanced, and mitochondrial morphology and function was impaired, which resulted in the reduced exercise capacity. There were no differences in the known protein associated with iron homeostasis in mitochondria. In the analysis by protein interaction, we found that mitoNEET combined with cytosolic protein X associated with iron homeostasis and mitochondrial inner membrane protein Y associated with transportation of some substances into mitochondria.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (33 results)

All 2016 2015 2014

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Acknowledgement Compliant: 7 results,  Open Access: 2 results) Presentation (17 results) (of which Int'l Joint Research: 10 results,  Invited: 1 results) Book (2 results)

  • [Journal Article] The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes.2016

    • Author(s)
      Mizushima, W., Takahashi , H., Watanabe, M., Kinugawa, S., Matsushima, S., Takada, S., Yokota, T., Furihata, T., Matsumoto, J., Tsuda, M., Chiba, I., Nagashima, S., Yanagi, S., Matsumoto, M., Nakayama, K.I., Tsutsui, H. and Hatakeyama, S.
    • Journal Title

      J. Mol. Cell. Cardiol.

      Volume: 100 Pages: 43-53

    • DOI

      10.1016/j.yjmcc.2016.09.013

    • NAID

      120006360069

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling.2016

    • Author(s)
      Matsushima S, Kuroda J, Zhai P, Liu T, Ikeda S, Nagarajan N, Oka S, Yokota T, Kinugawa S, Hsu C, Li H , Tsutsui H, Sadoshima J.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 126 Issue: 9 Pages: 3403-3416

    • DOI

      10.1172/jci85624

    • NAID

      120006809287

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dipeptidyl peptidase-4 inhibitor improved exercise capacity and mitochondrial biogenesis in mice with heart failure via activation of GLP-1 receptor signaling.2016

    • Author(s)
      Takada S, Masaki Y, Kinugawa S, Matsumoto J, Furihata T, Mizushima W, Kadoguchi T, Fukushima A, Homma T, Takahashi M, Harashima S, Matsushima S, Yokota T, Tanaka S, Okita K, Tsutsui H
    • Journal Title

      Cardiovasc Res

      Volume: 111 Issue: 4 Pages: 338-347

    • DOI

      10.1093/cvr/cvw182

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Direct renin inhibitor ameliorated insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.2016

    • Author(s)
      Fukushima A, Kinugawa S, Takada S, Matsumoto J, Furihata T, Mizushima W, Tsuda M, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Journal Title

      Eur J Pharmacol

      Volume: 779 Pages: 147-156

    • DOI

      10.1016/j.ejphar.2016.03.022

    • NAID

      120006219992

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Skeletal Muscle Abnormalities in Heart Failure2015

    • Author(s)
      Kinugawa S, Takada S, Matsushima S, Okita K, Tsutsui H
    • Journal Title

      International Heart Journal

      Volume: 56 Issue: 5 Pages: 475-484

    • DOI

      10.1536/ihj.15-108

    • NAID

      130005102118

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Curcumin ameliorates skeletal muscle atrophy in type I diabetic mice via inhibiting the protein ubiqutination2015

    • Author(s)
      Ono T, Takada S, Kinugawa S, Tsutsui H
    • Journal Title

      Exp Physiol

      Volume: 100 Issue: 9 Pages: 1052-1063

    • DOI

      10.1113/ep085049

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress.2015

    • Author(s)
      Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, Fukushima A, Matsushima S, Yokota T, Kinugawa S, Tsutsui H
    • Journal Title

      Nephrol Dial Transplant.

      Volume: in press Issue: 6 Pages: 182-188

    • DOI

      10.1093/ndt/gfv103

    • NAID

      120005743055

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low-intensity exercise under ischemic conditions enhances metabolic stress in patients with heart failure2015

    • Author(s)
      Takahashi M, Kinugawa S, Takada S, Hirabayashi K, Yokota T, Matsushima S, Saito A, Okita K, Tsutsui H
    • Journal Title

      Int J Cardiol

      Volume: 201 Pages: 142-4

    • DOI

      10.1016/j.ijcard.2015.08.022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Serum brain-derived neurotrophic factor level predicts adverse clinical outcomes in patients with heart failure2015

    • Author(s)
      Fukushima A, Kinugawa S, Homma T, Masaki Y, Furihata T, Yokota T, Matsushima S, Takada S, Kadoguchi T, Oba K, Okita K, Tsutsui H
    • Journal Title

      J Card Fail

      Volume: 21 Issue: 4 Pages: 300-306

    • DOI

      10.1016/j.cardfail.2015.01.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle.2015

    • Author(s)
      Kadoguchi T, Kinugawa S, Takada S, Fukushima A, Furihata T, Homma T, Masaki Y, Mizushima W, Nishikawa M, Takahashi M, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Journal Title

      Exp Physiol

      Volume: 100 Issue: 3 Pages: 312-322

    • DOI

      10.1113/expphysiol.2014.084095

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Intramyocellular lipid is increased in the skeletal muscle of patients with dilated cardiomyopathy with lowered exercise capacity.2014

    • Author(s)
      Hirabayashi K, Kinugawa S, Yokota T, Takada S, Fukushima A, Suga T, Takahashi M, Ono T, Morita N, Omokawa M, Harada K, Oyama-Manabe N, Shirato H, Matsushima S, Okita K, Tsutsui H
    • Journal Title

      International Journal of Cardiology

      Volume: 176 Issue: 3 Pages: 1110-1112

    • DOI

      10.1016/j.ijcard.2014.07.113

    • NAID

      120006809251

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] (Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice2014

    • Author(s)
      Fukushima A, Kinugawa S, Takada S, Matsushima S, Sobirin MA, Ono T, Takahashi M, Suga T, Homma T, Masaki Y, Furihata T, Kadoguchi T, Yokota T, Okita K, Tsutsui H
    • Journal Title

      American Journal of Physiology Endocrinology and Metabolism

      Volume: 307 Issue: 6 Pages: E503-E514

    • DOI

      10.1152/ajpendo.00449.2013

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.2014

    • Author(s)
      Takada S, Hirabayashi K, Kinugawa S, Yokota T, Matsushima S, Suga T, Kadoguchi T, Fukushima A, Homma T, Mizushima W, Masaki Y, Furihata T, Katsuyama R, Okita K, Tsutsui H
    • Journal Title

      European Journal of Pharmacology

      Volume: 740 Pages: 690-696

    • DOI

      10.1016/j.ejphar.2014.06.008

    • NAID

      120005476207

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.2014

    • Author(s)
      Suga T, Kinugawa S, Takada S, Kadoguchi T, Fukushima A, Homma T, Masaki Y, Furihata T, Takahashi M, Sobirin MA, Ono T, Hirabayashi K, Yokota T, Tanaka S, Okita K, Tsutsui H.
    • Journal Title

      Endocrinology

      Volume: 155 Issue: 1 Pages: 68-80

    • DOI

      10.1210/en.2013-1382

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Mitochondrial protein acetylation in skeletal muscle was associated with exercise intolerance in heart failure after myocardial infarction.2016

    • Author(s)
      Tsuda M, Kinugawa S, Takada S, Fukushima A, Yokota T, Mizushima W, Furihata T, Matsumoto J, Katayama T, Nakajima T, Maekawa S, Nambu H, Shirakawa R, Kakutani N, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2016.
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Brain-derived neurotrophic factor plays an important role of exercise capacity and mitochondrial function in the skeletal muscle in mice with post-infarct heart failure.2016

    • Author(s)
      Nakajima T, Kinugawa S, Matsumoto J, Takada S, Furihata T, Tsuda M, Katayama T, Nambu H, Shirakawa R, Maekawa S, Kakutani N, Mizushima W, Yokota T, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2016.
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The activation of glucagon-like peptide-1 improves the mitochondrial abnormalities in skeletal muscle and exercise intolerance in heart failure mice.2016

    • Author(s)
      Katayama T, Takada S, Masaki Y, Kinugawa S, Matsumoto J, Nakajima T, Tsuda M, Furihata T, Mizushima W, Fukushima A, Yokota T, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2016
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Brain-derived neurotrophic factor improves exercise capacity and mitochondrial function in skeletal muscles of mice with heart failure via AMPK-PGC1α signaling.2016

    • Author(s)
      Matsumoto J, Takada S, Furihata T, Tsuda M, Nakajima T, Katayama T, Yokota T, Kinugawa S
    • Organizer
      The 33rd Annual Meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      東京コンベンションホール(東京都特別区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mitoNEET regulates mitochondrial iron contents in the heart2016

    • Author(s)
      Maekawa S, Furihata T, Takada S, Fukushima A, Tsuda M, Matsumoto J, Yokota T, Kinugawa S
    • Organizer
      The 33rd Annual Meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      東京コンベンションホール(東京都特別区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mitochondral iron homeostatis in the heart2016

    • Author(s)
      降旗高明,絹川真太郎
    • Organizer
      第20回日本心不全学会学術集会
    • Place of Presentation
      ロイトン札幌(札幌市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Desruption of mitoNEET, outer mitochondrial membrane protein, increases mitochondrial iron content in the heart2015

    • Author(s)
      Furihata T, Kinugawa S, Takada S, Matsushima S, Mizushima W, Yokota T, Tsutsui H
    • Organizer
      Desruption of mitoNEET, outer mitochondrial membrane protein, increases mitochondrial iron content in the heart
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Decreased brain-derived neurotrophic factor impairs mitochondrial function via ampk-pgc1a signaling in the skeletal muscle from post-infarct heart failure mice2015

    • Author(s)
      Matsumoto J, Kinugawa S, Takada S, Furihata T, Mizushima W, Matsushima S, Yokota T, Tsutsui H
    • Organizer
      The 32nd Annual Meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain-derived neurotrophic factor could regulate mitochondrial function in the skeletal muscle through ampk-pgc1a signaling in heart failure mice2015

    • Author(s)
      Matsumoto J, Kinugawa S, Takada S, Furihata T, Mizushima W, Tsuda M, Nakajima T, Katayama T, Fukuoka R, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2015
    • Place of Presentation
      Orlando(USA)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Deletion of NAD(P)H oxidase 2 attenuates angiotensin II-induced skeletal muscle atrophy2015

    • Author(s)
      Mizushima W, Kinugawa S, Kadoguchi T, Takada S, Fukushima A, Furihata T, Matsumoto J, Tsuda M, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2015
    • Place of Presentation
      Orlando(USA)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Recombinant human BDNF can mimic effects of exercise training in mice2015

    • Author(s)
      Takada S, Kinugawa S, Matsushima S, Yokota T, Mizushima W, Furihata T, Matsumoto J, Tsuda M, Fukushima A, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2015
    • Place of Presentation
      Orlando(USA)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Disruption of outer mitochondrial membrane protein, mitoNEET, increases mitochondrial iron content in the heart.2014

    • Author(s)
      Furihata T, Kinugawa S, Matsushima S, Takada S, Fukushima A, Mizushima W, Kadoguchi T, Masaki Y, Yokota T, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2014
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Angiotensin II directly induces mitochondrial dysfunction and atrophy in the skeletal muscle.2014

    • Author(s)
      Kadoguchi T, Kinugawa S, Fukushima A, Furihata T, Suga T, Takada S, Mizushima W, Kudo M, Matsumoto J, Tsuda M, Nishikawa M, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2014.
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Brain-derived neurotrophic factor maintains exercise capacity and mitochondrial function in the skeletal muscle through AMPK-PGC-1α signaling2014

    • Author(s)
      Takada S, Kinugawa S, Matsushima S, Mizushima W, Fukushima A, Furihata T, Kadoguchi T, Yokota T, Suga T, Okita K, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2014.
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] AST-120 ameliorates lowered exercise capacity and mitochondrial dysfunction of the skeletal muscle in mice with chronic kidney disease via reducing oxidative stress2014

    • Author(s)
      Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, Fukushima A, Matsushima S, Yokota T, Kinugawa S, Tsutsui H
    • Organizer
      American Heart Association Scientific Session 2014.
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Sesamin improves lowered exercise capacity, mitochondrial dysfunction in the skeletal muscle from high fat diet-induced diabetis mice2014

    • Author(s)
      Takada S, Kinugawa S, Takemoto D, Masaki Y, Kadoguchi T, Yokota T, Matsushima S, Fukushima A, Homma T, Furihata T, Suga T, Katsuyama R, Ono Y, Shibata H, Okita K, Tsutsui H
    • Organizer
      50th European Association for the Study of Diabetes Annual Meetings
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2014-09-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Dipeptidyl peptidase-4 inhibitor improved exercise capacity in association with switching to oxidative skeletal muscle fiber type in mice with post-infarct heart failure2014

    • Author(s)
      Masaki Y, Kinugawa S, Takada S, Kadoguchi T, Fukushima A, Homma T, Furihata T, Katsuyama R, Suga T, Takahashi M, Yokota T, Matsushima S, Okita K, Tsutsui H
    • Organizer
      74th American Diabetic Association Scientific Seissions
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-06-14
    • Related Report
      2014 Research-status Report
  • [Book] 心不全診療の極意2016

    • Author(s)
      絹川真太郎、福島新
    • Total Pages
      180
    • Publisher
      南山堂
    • Related Report
      2016 Annual Research Report
  • [Book] 心不全における骨格筋の重要性・臨床心不全のいちばん大事なところ602014

    • Author(s)
      絹川真太郎
    • Total Pages
      351
    • Publisher
      メディカ出版
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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