Regulation and physiological role of mitochondrial fusion and fission in mammals

• Project/Area Number: 26291044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kurume University
• Principal Investigator: Naotada Ishihara 久留米大学, 分子生命科学研究所, 教授 (10325516)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: ミトコンドリア / オルガネラ / 膜融合 / 膜分裂 / GTPase / 細胞・組織 / 生体分子 / 膜形成

Outline of Final Research Achievements

Mitochondrial dynamics by frequent fusion and fission have important roles in various cellular signaling processes and pathophysiology in vivo. However, the molecular mechanism that regulates mitochondrial fusion and fission in mammalian cells are not well understood. We analyzed molecular mechanism to regulate mitochondrial morphology in mammalian cells, by balanced mitochondrial fusion and fission. We also found important roles of mitochondrial fission in formation of cardiomyocytes during neonatal heart development, and maintenance of oocyte quality.

Research Products

• [Journal Article] PARL paves the way to apoptosis. (2017)
  • Author(s): N. Ishihara and K. Mihara.
  • Journal Title: Nat. Cell Biol. Volume: 19 Issue: 4 Pages: 263-265
  • DOI: 10.1038/ncb3504
  • Int'l Joint Research
• [Journal Article] ミトコンドリア形態変化の生理的意義 (2017)
  • Author(s): 伴 匡人、尾上 健太、石原 直忠
  • Journal Title: 医学のあゆみ Volume: 260 Pages: 18-23
  • Peer Reviewed
• [Journal Article] D-Glutamate is metabolized in the heart mitochondria. (2016)
  • Author(s): M. Ariyoshi, M. Katane, K. Hamase, Y. Miyoshi, M. Nakane, A. Hoshino, Y. Okawa, Y. Mita, S. Kaimoto, M. Uchihashi, K. Fukai, K. Ono, S. Tateishi, D. Hato, R. Yamanaka, S. Honda, Y. Fushimura, E. Iwai-Kanai, N. Ishihara, M. Mita, H. Homma, and S. Matoba.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 43911-43911
  • DOI: 10.1038/srep43911
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct types of protease systems are involved in homeostasis regulation of mitochondrial morphology via balanced fusion and fission. (2016)
  • Author(s): Saita S, Ishihara T, Maeda M, Iemura S, Natsume T, Mihara K, Ishihara N.
  • Journal Title: Genes Cells Volume: 21(5) Issue: 5 Pages: 408-424
  • DOI: 10.1111/gtc.12351
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinct types of protease systems are involved in homeostasis regulation of mitochondrial morphology via balanced fusion and fission. (2016)
  • Author(s): S. Saita, T. Ishihara, M.Maeda, S. Iemura, T. Natsume, K. Mihara and N. Ishihara.
  • Journal Title: Genes Cells. Volume: 21 Issue: 1 Pages: 408-424
  • DOI: 10.1038/srep28331
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. (2016)
  • Author(s): B. Oettinghaus, J. Schulz, L. Restelli, C. Savoia, A. Schmidt, K. Schmitt, A. Grimm, L. Morè, J. Hench, M. Tolnay, A. Eckert, P. D'Adamo, P. Franken, N. Ishihara, K. Mihara, J. Bischofberger, L. Scorrano, S. Frank.
  • Journal Title: Cell Death Differ. Volume: 23 Issue: 1 Pages: 18-28
  • DOI: 10.1038/cdd.2015.39
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ミトコンドリアのダイナミクスとその生理機能 (2016)
  • Author(s): 太田 あずさ、伴 匡人、石原 直忠
  • Journal Title: 脳21 Volume: 19 Pages: 211-216
• [Journal Article] COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1. (2015)
  • Author(s): Ban-Ishihara R, Tomohiro-Takamiya S, Tani M, Baudier J, Ishihara N, and Kuge O
  • Journal Title: FEBS Lett Volume: 589 Issue: 20PartB Pages: 3126-3132
  • DOI: 10.1016/j.febslet.2015.08.039
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration. (2015)
  • Author(s): Wang L, Ishihara T, Ibayashi Y, Tatsushima K, Setoyama D, Hanada Y, Takeichi Y, Sakamoto S, Yokota S, Mihara K, Kang D, Ishihara N, Takayanagi R, Nomura M
  • Journal Title: Diabetologia Volume: 58 Issue: 10 Pages: 2371-2380
  • DOI: 10.1007/s00125-015-3704-7
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CDK5 phosphorylates DRP1 and drives mitochondrial defects in NMDA-induced neuronal death. (2015)
  • Author(s): A. Jahani-Asl, E. Huang, I. Irrcher, J. Rashidian, N. Ishihara, DC. Lagace, RS. Slack, DS. Park.
  • Journal Title: Hum. Mol. Genet. Volume: 24 Issue: 16 Pages: 4573-4583
  • DOI: 10.1093/hmg/ddv188
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Physiological roles of mitochondrial fission in cultured cells and mouse development. (2015)
  • Author(s): Ishihara T, Kohno H, Ishihara N.
  • Journal Title: Ann N Y Acad Sci. Volume: 1350 Issue: 1 Pages: 77-81
  • DOI: 10.1111/nyas.12848
  • Peer Reviewed
• [Journal Article] ミトコンドリア分裂の生理機能とその破綻 (2015)
  • Author(s): 石原 直忠
  • Journal Title: 医学のあゆみ Volume: 254 Pages: 433-439
• [Journal Article] ミトコンドリアのダイナミクスとその役割 (2015)
  • Author(s): 石原 直忠
  • Journal Title: 数研出版 サイエンスネット Volume: 52 Pages: 2-5
• [Journal Article] Dynamics of mtDNA nucleoids regulated by mitochondrial fission is essential for maintenance of homogeneously active mitochondria during neonatal heart development. (2015)
  • Author(s): T. Ishihara, R. Ban-Ishihara, M. Maeda, Y. Matsunaga, A. Ichimura, S. Kyogoku, H. Aoki, S. Katadam K. Nakada, M. Nomura, N. Mizushima, K. Mihara, and N. Ishihara
  • Journal Title: Molecular Cell Biology Volume: 35 Issue: 1 Pages: 211-223
  • DOI: 10.1128/mcb.01054-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division. (2015)
  • Author(s): Arasaki K., Shimizu H., Mogari H., Nishida N., Hirota N., Furuno A., Kudo Y., Baba M., Baba N., Cheng J., Fujimoto T., Ishihara N., Ortiz-Sandoval C., Barlow L., Raturi A., Dohmae N., Wakana Y., Inoue H., Tani K., Dacks J., Simmen T., Tagaya M.
  • Journal Title: Dev. Cell. Volume: 32 Pages: 304-317
  • Peer Reviewed
• [Journal Article] ミトコンドリア分裂因子Drp1は細胞小器官のダイナミックな再編成を通して卵子の質を維持する (2015)
  • Author(s): 宇田川 理、石原 直忠
  • Journal Title: 細胞工学 Volume: 34 Pages: 82-83
• [Journal Article] ミトコンドリアの融合と分裂：その意義と制御機構 (2015)
  • Author(s): 伴 匡人、後藤 雅史、石原 直忠
  • Journal Title: 化学と生物 Volume: 53 Pages: 27-33
  • NAID: 130005113831
• [Journal Article] Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. (2015)
  • Author(s): Oettinghaus B., Schulz J., Restelli L., Savoia C., Schmidt A., Schmitt K., Grimm A., Morè L., Hench J., Tolnay M., Eckert A., D'Adamo P., Franken P., Ishihara N., Mihara K., Bischofberger J., Scorrano L. Frank S.
  • Journal Title: Cell Death Differ. Volume: 未
  • Peer Reviewed
• [Journal Article] Mitochondrial Fission Factor Drp1 Maintains Oocyte Quality via Dynamic Rearrangement of Multiple Organelles (2014)
  • Author(s): O Udagawa, T Ishihara, M Maeda, Y Matsunaga, S Tsukamoto, N Kawano, K Miyado, H Shitara, S Yokota, M Nomura, K Mihara, N Mizushima, N Ishihara
  • Journal Title: Current Biology Volume: 24 Issue: 20 Pages: 2451-2458
  • DOI: 10.1016/j.cub.2014.08.060
  • Peer Reviewed / Open Access
• [Journal Article] 細胞と組織におけるミトコンドリアの形態制御機構と役割 (2014)
  • Author(s): 石原 孝也、石原 直忠
  • Journal Title: 生体の科学 Volume: 65 Pages: 299-303
• [Presentation] Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin (2017)
  • Author(s): Tadato Ban and Naotada Ishihara
  • Organizer: International Symposium on Autophagy
  • Int'l Joint Research
• [Presentation] ミトコンドリアの膜とゲノムの協調的な形態制御 (2016)
  • Author(s): 伴匡人、石原孝也、太田あずさ、石原直忠
  • Organizer: 第３９回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-02
  • Invited
• [Presentation] 成長期の骨格筋におけるDrp1の機能 (2016)
  • Author(s): 一村 紋佳、石原 孝也、石原 直忠
  • Organizer: 第３９回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] ミトコンドリアの膜とmtDNAのダイナミクスを制御する因子の探索 (2016)
  • Author(s): 石原 孝也、石原 直忠
  • Organizer: 第３９回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] OPA1プロテオリポソームによるミトコンドリア内膜融合機構の解明 (2016)
  • Author(s): 伴匡人、石原直忠
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-27
• [Presentation] ミトコンドリアのGTPaseタンパク質による融合と分裂の制御 (2016)
  • Author(s): 石原直忠、河野裕翔、太田あずさ、伴匡人、石原孝也
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-26
• [Presentation] ミトコンドリアの融合と分裂のバランス制御とその分子機構 (2016)
  • Author(s): 石原直忠、伴匡人、河野裕翔、石原孝也
  • Organizer: 第68回日本細胞生物学会大会
  • Place of Presentation: 京都
  • Year and Date: 2016-06-16
  • Invited
• [Presentation] 個体内でのミトコンドリアの融合と分裂の意義 (2016)
  • Author(s): 石原 直忠
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-11
  • Invited
• [Presentation] ミトコンドリアの動的な形態制御とその意義 (2016)
  • Author(s): 石原 直忠
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] ミトコンドリアの膜とDNAの協調的かつ動的な制御機構 (2015)
  • Author(s): 石原 孝也、石原 直忠
  • Organizer: BMB2015（第38回日本分子生物学会、第88回日本生化学会)
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] ミトコンドリアは生きている (2015)
  • Author(s): 石原 直忠
  • Organizer: 第15回日本ミトコンドリア学会年会 市民公開講座
  • Place of Presentation: 福井
  • Year and Date: 2015-11-21
  • Invited
• [Presentation] オーバービュー（基礎科学） (2015)
  • Author(s): 石原 直忠
  • Organizer: 第15回日本ミトコンドリア学会年会
  • Place of Presentation: 福井
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] Roles of mitochondrial dynamics in mammalian development/differentiation. Molecular Mitochondria (2015)
  • Author(s): Naotada Ishihara
  • Organizer: Joint Seminar of Young Finnish‐Japanese Mitoscientists
  • Place of Presentation: Helsinki
  • Year and Date: 2015-10-05
  • Int'l Joint Research / Invited
• [Presentation] ミトコンドリアの動的な形態制御 (2015)
  • Author(s): 石原 直忠
  • Organizer: 第45回(2015)新潟神経学夏期セミナー
  • Place of Presentation: 新潟
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] 哺乳動物細胞におけるミトコンドリアの融合と分裂の制御 (2015)
  • Author(s): 石原 直忠
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
  • Invited
• [Presentation] ミトコンドリア核様体ダイナミクスの分子機構の解明 (2015)
  • Author(s): 石原（伴）玲子，石原 直忠
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] ミトコンドリアの融合と分裂の生理的意 (2015)
  • Author(s): 石原 直忠
  • Organizer: 第120回日本解剖学会総会・全国学術集会、第92回日本生理学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21
  • Invited
• [Presentation] リコンビナントOPA1Lによるミトコンドリア内膜融合機構の解明 (2014)
  • Author(s): 伴匡人、石原直忠
  • Organizer: 第14回日本ミトコンドリア学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-03 – 2014-12-05
• [Presentation] ミトコンドリア核様体ダイナミクスの分子機構の解析 (2014)
  • Author(s): 石原玲子、石原直忠
  • Organizer: 第14回日本ミトコンドリア学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-03 – 2014-12-05
• [Presentation] mtDNA分布制御を介した心筋細胞成熟におけるミトコンドリア分裂の役割 (2014)
  • Author(s): 石原孝也、石原玲子、一村紋佳、三原勝芳、石原直忠
  • Organizer: 第14回日本ミトコンドリア学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-12-03 – 2014-12-05
• [Presentation] Physiological roles of mitochondrial fission in cultured cells and in mice development (2014)
  • Author(s): Naotada Ishihara, Reiko Ban-Ishihara, Takaya Ishihara, Tadato Ban
  • Organizer: 11th Conference of the Asian Society of Mitochondrial Research and Medicine (ASMRM 2014)
  • Place of Presentation: Taipei
  • Year and Date: 2014-11-14
  • Invited
• [Presentation] ミトコンドリアのダイナミクスによる細胞機能制御 (2014)
  • Author(s): 石原直忠、伴匡人、石原孝也、石原（伴）玲子、前田 真希
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] OPA1プロテオリポソームによるミトコンドリア内膜融合機構の解明 (2014)
  • Author(s): 伴匡人、石原直忠
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Dynamics of mtDNA nucleoid regulated by mitochondrial fission contributes to cristae reformation, release of cytochrome c, and heart development (2014)
  • Author(s): Takaya Ishihara, Reiko Ban-Ishihara and Naotada Ishihara
  • Organizer: EuroMit 2014
  • Place of Presentation: Tampere, Finland
  • Year and Date: 2014-06-15 – 2014-06-19
• [Presentation] 哺乳動物細胞におけるミトコンドリアの融合と分裂の制御 (2014)
  • Author(s): 細田將太郎、石原孝也、石原（伴）玲子、伴匡人、石原直忠
  • Organizer: 第66回日本細胞生物学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-12
• [Remarks] 久留米大学 分子生命科学研究所 高分子化学研究部門
  • URL: http://mitochondria.jp/
• [Remarks] 久留米大学 分子生命科学研究所
  • URL: http://www.lsi.kurume-u.ac.jp/