Regulation and biological significance of mitochondrial c-Src.

• Project/Area Number: 26460372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Fukushima Medical University
• Principal Investigator: Homma Yoshimi 福島県立医科大学, 医学部, 教授 (60192324)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミトコンドリア / 活性酸素 / チロシンキナーゼ / B細胞 / リン酸化 / プロテオーム解析 / トランスジェニックマウス / Ｂ細胞 / シグナル伝達 / プロテオーム

Outline of Final Research Achievements

Suppression of c-Src activity enhances production of radical oxygen species (ROS) in mitochondria. We identified flotillin-1 as a c-Src substrate that prevent ROS production. We produced transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in B cells. Splenic B cells in male, but not female, Tg mice produced enhanced ROS, and exhibited decreased humoral immune response.

Research Products

• [Journal Article] Mitochondrial reactive oxygen species suppress humoral immune response through reduction of CD19 expression in B cells in mice (2017)
  • Author(s): Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K. Homma, Tomohiro Kurosaki, Yoshimi Homma
  • Journal Title: Eur J Immunol Volume: 47 Issue: 2 Pages: 406-418
  • DOI: 10.1002/eji.201646342
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Synthesis of prenylated quinolinecarboxylic acid derivatives and their anti-obesity activities (2015)
  • Author(s): Haruhisa Kikuchi, Toshiyuki Suzuki, Masato Ogura, Miwako K. Homma, Yoshimi Homma, Yoshiteru Oshima
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 23 Issue: 1 Pages: 66-72
  • DOI: 10.1016/j.bmc.2014.11.024
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold. (2015)
  • Author(s): Suzuki T, Kikuchi H, Ogura M, Homma MK, Oshima Y, Homma Y.
  • Journal Title: PLoS One Volume: 10 Issue: 2 Pages: e0117088-e0117088
  • DOI: 10.1371/journal.pone.0117088
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphorylation of flotillin-1 by mitochondrial c-Src is required to prevent the production of reactive oxygen species. (2014)
  • Author(s): Ogura M, Yamaki J, Homma MK, Homma Y.
  • Journal Title: FEBS Lett Volume: 588 Issue: 17 Pages: 2837-2843
  • DOI: 10.1016/j.febslet.2014.06.044
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Enhanced metabolic ROS production by a loss of protein phosphorylation in mitochondria (2016)
  • Author(s): Yoshimi Homma
  • Organizer: 21st International CH Symposium on Cancer Research
  • Place of Presentation: Moscow
  • Year and Date: 2016-05-25
  • Int'l Joint Research / Invited