The role of mitochondrial protein MENT in myocardial ischemic preconditioning

• Project/Area Number: 26860559
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Kioka Hidetaka 大阪大学, 医学(系)研究科(研究院), 寄附講座助教 (70642099)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心筋虚血 / ミトコンドリア / エネルギー代謝 / エネルギーー代謝 / ATP / プレコンディショニング / イメージング

Outline of Final Research Achievements

Most eukaryotic cells generate ATP through oxidative phosphorylation system (OXPHOS) to support cellular activities. We have recently established the method for the selective measurement of intra-mitochondrial ATP levels and have identified the hypoxia-inducible protein MENT as a positive regulator of OXPHOS by cultured cell-based experiments. In this study, we introduced a FRET-based ATP biosensor named ATeam into zebrafish heart and examined in vivo role of MENT under hypoxia. We established the in vivo ATP imaging technique. This technique clearly revealed that MENT-expressing cardiomyocyte populations showed preserved contractility with increased intra-mitochondrial ATP concentration in hypoxic condition.　Futhermore, we showed that MENT expression is enhanced in the risk area in canine ischemic preconditioning model. These results suggest that MENT functions as a guardian of hypoxic tissue and could become a therapeutic target for hypoxia-related diseases.

Research Products

• [Journal Article] A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure. (2016)
  • Author(s): 1.M. Kanzaki, Y. Asano, H. Ishibashi-Ueda, E, Oiki, T. Nishida, H. Asanuma, H. Kato, Y. Oka, T. Ohtani, O. Tsukamoto, S. Higo, H. Kioka, K. Matsuoka, Y. Sawa, I. Komuro, M. Kitakaze, S. Takashima, Y. Sakata.
  • Journal Title: PLoS One. Volume: 11
  • Peer Reviewed / Open Access
• [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5. (2015)
  • Author(s): Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 6137-6137
  • DOI: 10.1038/ncomms7137
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase (2015)
  • Author(s): T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
  • Journal Title: Proc. Nat. Acad. Sci. U.S.A. Volume: 112 Issue: 5 Pages: 1553-1558
  • DOI: 10.1073/pnas.1419767112
  • Peer Reviewed / Open Access
• [Journal Article] Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. (2014)
  • Author(s): Shintani Y, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, Takashima S, Yashiro K, Suzuki K.
  • Journal Title: EMBO Reports Volume: 15 Issue: 4 Pages: 438-445
  • DOI: 10.1002/embr.201337945
  • Peer Reviewed / Open Access
• [Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart. (2014)
  • Author(s): Matsuoka K, Asano Y, Higo S, Tsukamoto O, Yan Y, Yamazaki S, Matsuzaki T, Kioka H, Kato H, Uno Y, Asakura M, Asanuma H, Minamino T, Aburatani H, Kitakaze M, Komuro I, Takashima S.
  • Journal Title: FASEB J. Volume: 28(4) Issue: 4 Pages: 1870-9
  • DOI: 10.1096/fj.13-245522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] In vivo Visualization of ATP Dynamics Under Hypoxia Reveals That G0/G1 Switch Gene 2 Provides Ischemic Tolerance Through the Increase of ATP Production (2014)
  • Author(s): Hidetaka Kioka, Hisakazu Kato, Yoshihiro Asano, Yasushi Sakata, Masafumi Kitakaze, Seiji Takashima.
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: Chicago, Illinois,USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Remarks] 大阪大学大学院医学系研究科循環器内科学
  • URL: http://www.cardiology.med.osaka-u.ac.jp/
• [Remarks] 大阪大学大学院医学系研究科医化学講座
  • URL: http://medbio.sakura.ne.jp/