Molecular mechanism of mitochondrial fission

• Project/Area Number: 25440088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: Otera Hidenori 九州大学, 医学(系)研究科(研究院), 助教 (40380612)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ミトコンドリア / アポトーシス / オルガネラ形態 / ミトコンドリアダイナミクス / クリステ構造 / ミトコンドリア分裂 / DRP1 / ミトコンドリア形態 / 膜分裂 / 高分子量GTPase / メンブレンダイナミクス

Outline of Final Research Achievements

Here, we analyzed the functional division of mitochondrial fission receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae-remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments that disrupt cristae morphology, such as OPA1-depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in both types of cells, revealing that the Drp1-MiD49/51 system limits cristae remodeling. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49 and MiD51 is epistatic to cristae-remodeling through disassembly of OPA1 oligomers and functions as an essential gatekeeper for intrinsic apoptosis.

Research Products

• [Journal Article] Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling (2016)
  • Author(s): Otera H, Miyata N, Kuge O, Mihara K
  • Journal Title: Journal of Cell Biology Volume: 212 Issue: 5 Pages: 531-544
  • DOI: 10.1083/jcb.201508099
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mitochondrial dynamics: Molecular mechanism and physiologic functions of mitochondrial fusion and fission (2016)
  • Author(s): Mihara K, Otera H
  • Journal Title: Encyclopedia of Cell Biology Volume: 2 Pages: 279-292
  • Acknowledgement Compliant
• [Journal Article] Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity (2014)
  • Author(s): Yoshizumi, T., Ichinohe, T., Sasaki, O., Otera, H., Kawabata, S., Mihara, K., and #Koshiba, T.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 4713-4713
  • DOI: 10.1038/ncomms5713
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] MiD49とMiD51を介したDrp1依存的ミトコンドリア分裂によるクリステ構造変化とシトクロムC放出制御 (2015)
  • Author(s): 大寺秀典、三原勝芳、宮田暖、久下理
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 哺乳動物に備わる２つのミトコンドリア分裂システムとアポトーシスにおける役割の違い (2015)
  • Author(s): 大寺秀典、三原勝芳、宮田暖、久下理
  • Organizer: 第１５回日本ミトコンドリア学会年会
  • Place of Presentation: 福井県国際交流会館
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] ミトコンドリア分裂におけるDrp1のリクルート機構 (2014)
  • Author(s): 大寺秀典、三原勝芳
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Book] 細胞工学 (2013)
  • Author(s): 大寺秀典
  • Total Pages: 6
  • Publisher: 学研メディカル秀潤社
• [Remarks] ミトコンドリアの分裂がアポトーシス（細胞の自殺）開始を制御する仕組みを解明
  • URL: http://www.med.kyushu-u.ac.jp/app/modules/information/detail.php?i=844&c=10