Analysis of a novel mitochondrial protein AMF in energy metabolism

• Project/Area Number: 25860599
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: KATO Hisakazu 大阪大学, 医学(系)研究科(研究院), 特任研究員 (30589312)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ミトコンドリア / ATP / 虚血 / 循環器・高血圧 / 分子心臓学 / エネルギー代謝

Outline of Final Research Achievements

Heart tissue consumes more energy than other organs to maintain cardiac pump function. Imbalances between energy demand and supply in an ischemic myocardium fall into the mechanical failure of heart. However, the mechanism by which mitochondrial ATP production is regulated under hypoxia is not fully understood. In this study, we revealed how a novel hypoxia-induced protein AMF affects mitochondrial ATP production under ischemic condition, mainly from the following experiments. (1) Immunoaffinity purification and mass spectrometric analysis revealed that AMF interacted with FoF1-ATP synthase complex. (2) Assessment of mitochondrial ATP concentration using FRET-based ATP biosensor allowed us to show that overexpression of AMF inhibited the decreases in mitochondrial ATP concentration under hypoxic condition in cultured cardiomyocytes and also in zebrafish heart. These results suggest that AMF functions as a guardian of ischemic heart via activating FoF1-ATP synthase.

Research Products

• [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] 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
• [Journal Article] Evaluation of intra-mitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation (2013)
  • Author(s): Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Tkafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y and Takashima S
  • Journal Title: PNAS Volume: 111 Issue: 1 Pages: 273-278
  • DOI: 10.1073/pnas.1318547111
  • Peer Reviewed / Open Access
• [Presentation] Evaluation of Mitochondrial ATP Levels in Vivo Identifies G0/G1 Switch Gene 2 as a Therapeutic Target of Ischemic Heart Failure (2014)
  • Author(s): Hisakazu KATO, Hidetaka KIOKA, Yoshihiro ASANO, Seiji TAKASHIMA
  • Organizer: 第18回日本心不全学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-11
• [Presentation] hypoxia-inducible protein MENT enhances mitochondrial ATP production by interacting with FoF1-ATP synthase (2013)
  • Author(s): Hisakazu KATO, Hidetaka Kioka, Makoto Fujikawa, Toshiharu Suzuki, Hiromi Imamura, Masasuke Yoshida, Yoshihiro Asano, Seiji Takashima
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸 ポートアイランド
• [Remarks] 大阪大学大学院医学系研究科・生命機能研究科 医化学講座
  • URL: http://medbio.sakura.ne.jp/
• [Remarks] 大阪大学大学院医学系研究科 医化学講座
  • URL: http://www.medbio.med.osaka-u.ac.jp/