Nerve injury-induced mitochondrial fission is involved in the maintenance of mitochondrial and axonal integrity

• Project/Area Number: 25430036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Nagoya University
• Principal Investigator: Kiryu-Seo Sumiko 名古屋大学, 医学(系)研究科(研究院), 准教授 (70311529)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ミトコンドリア / 神経再生 / 運動ニューロン / Drp1 / ミトコンドリア分裂 / 神経変性 / 軸索 / ATF3 / 神経損傷 / 軸索変性 / ミトコンドリアダイナミクス / ダイナミクス / 障害応答性

Outline of Final Research Achievements

Regenerating neurons are assumed to control mitochondrial dynamics properly to satisfy a huge energy demand and to maintain Ca2+ buffering. However, it is unclear how mitochondrial dynamics contributes to axonal and neuronal integrity in damaged neurons in vivo. We have found that short mitochondria are actively transported in regenerating motor nerves soon after nerve injury. The mice in which mitochondrial fission is ablated specifically in injured motor neurons have clarified that short mitochondria are divided mitochondria. Our study has demonstrated that acute and prominent mitochondrial fission is a crucial response during the early stage after nerve injury and is involved in the maintenance of mitochondrial and axonal integrity to prevent neurodegeneration.

Research Products

• [Journal Article] Motor nerve arborization requires proteolytic domain of Damage-induced neuronal endopeptidase (DINE) during development (2016)
  • Author(s): Matsumoto S, Kiryu-Seo S, Kiyama H
  • Journal Title: J Neurosci Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ECEL1 mutation implicates impaired axonal arborization of motor nerves in the pathogenesis of distal arthrogryposis (2016)
  • Author(s): Nagata K, Kiryu-Seo S, Tamada H, Okuyama-Uchimura F, Kiyama H, Saido TC
  • Journal Title: Acta Neuropathol Volume: in press
  • Peer Reviewed
• [Journal Article] Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin (2015)
  • Author(s): Yin X, Kiryu-Seo S, Kidd GJ, Feltri ML, Wrabetz L, Trapp BD
  • Journal Title: Glia Volume: 63 Issue: 1 Pages: 66-77
  • DOI: 10.1002/glia.22733
  • Peer Reviewed
• [Journal Article] microRNA-124 is down regulated in nerve injured motor neurons and it potentially targets mRNAs for KLF6 and STAT3 (2014)
  • Author(s): Nagata K, Hama I, Kiryu-Seo S and Kiyama H
  • Journal Title: Neuroscience Volume: 256 Pages: 426-432
  • DOI: 10.1016/j.neuroscience.2013.10.055
  • Peer Reviewed
• [Journal Article] ミエリンと軸索ホメオスタシス (2013)
  • Author(s): 桐生寿美子、木山博資
  • Journal Title: 脳21 Volume: 16 Pages: 26-30
• [Journal Article] 運動神経軸索再生とプロテアーゼ (2013)
  • Author(s): 木山博資、桐生寿美子、松本早紀子
  • Journal Title: Peripheral nerve Volume: 24 Pages: 214-218
• [Presentation] The mitochondrial dynamics after neuronal injury (2015)
  • Author(s): Sumiko Kiryu-Seo, Hiroshi Kiyama
  • Organizer: INS2015
  • Place of Presentation: Cains (Australia)
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Mitochondrial dynamics in damaged neurons (2015)
  • Author(s): 桐生寿美子、木山博資
  • Organizer: 第120回日本解剖学会総会、第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場 （兵庫県神戸市）
  • Year and Date: 2015-03-21
• [Presentation] DINE functions as a protease required for the motor nerve terminal arborization and neuromuscular junction formation (2015)
  • Author(s): 松本早紀子、桐生寿美子、木山博資
  • Organizer: 第120回日本解剖学会総会、第92回日本生理学会大会
  • Place of Presentation: 神戸国展示場 （兵庫県神戸市）
  • Year and Date: 2015-03-21
• [Presentation] Nerve injury-induced mitochondrial fission is an essential adaptive response to maintain neuronal survival and promote axonal regeneration (2014)
  • Author(s): Sumiko Kiryu-Seo, Hiromi Tamada, Yukina Kato, Naotada Ishihara, Masatoshi Nomura, Katsuyoshi Mihara, Hiroshi Kiyama
  • Organizer: Neuroscience 2014
  • Place of Presentation: Washington D.C. (USA)
  • Year and Date: 2014-11-18
• [Presentation] Enzymatic activity of Damage-induced neuronal endopeptidase/Endothelin-converting enzyme-like 1 (DINE/ECEL1) is crucial for neuromuscular junction formation during development. (2014)
  • Author(s): Sakiko Matsumoto, Sumiko Kiryu-Seo, Hiroshi Kiyama
  • Organizer: Neuroscience 2014
  • Place of Presentation: Washington D.C. (USA)
  • Year and Date: 2014-11-16
• [Presentation] 神経損傷に応答するミトコンドリア (2014)
  • Author(s): 桐生寿美子、木山博資
  • Organizer: 第57回日本神経化学会大会
  • Place of Presentation: 奈良県文化会館（奈良県奈良市）
  • Year and Date: 2014-09-29
• [Presentation] DINEのプロテアーゼ活性は脊髄運動ニューロン軸索終末分枝及び神経筋接合部形成に必須である (2014)
  • Author(s): 松本早紀子、桐生寿美子、木山博資
  • Organizer: 第57回日本神経化学会大会
  • Place of Presentation: 奈良県文化会館（奈良県奈良市）
  • Year and Date: 2014-09-29
• [Presentation] The protease activity of DINE/ECEL1 is required for the motor nerve terminal arborization and the neuromuscular junction formation (2014)
  • Author(s): Matsumoto S, Kiryu-Seo S, Kiyama H.
  • Organizer: 6th special conference of the international society for neurochemistry
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2014-09-21
• [Presentation] Aberrant axonal arborization of motor nerves in Damage-Induced Neuronal Endopeptidase deficient limb (2014)
  • Author(s): Nagata K, Kiryu-Seo S, Kiyama H, Saido TC.
  • Organizer: Cold spring harbor meeting
  • Place of Presentation: New York (USA)
  • Year and Date: 2014-09-16 – 2014-09-20
• [Presentation] 軸索に存在するDINEはシュワン細胞と相互作用することにより適切な軸索ブランチングおよび神経筋接合部形成を促す
  • Author(s): 桐生寿美子、松本早紀子、木山博資
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都市）
• [Presentation] DINE欠損運動神経の骨格筋支配の発生学的異常
  • Author(s): 永田健一、桐生寿美子、斉藤貴志、木山博資、西道隆臣
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都市）
• [Presentation] 神経再生・変性に関わるミトコンドリアダイナミクス
  • Author(s): 桐生寿美子、木山博資
  • Organizer: 脳内環境夏の班会議
  • Place of Presentation: 京都大学医学部紫欄会館（京都市）
• [Presentation] 神経損傷とミトコンドリア
  • Author(s): 桐生寿美子、木山博資
  • Organizer: 脳内環境冬の班会議
  • Place of Presentation: 東京ガーデンパレス（東京都文京区）
• [Presentation] 脊髄運動ニューロンの軸索最終分枝及び神経筋接合部形成にはDINEのプロテアーゼ活性が必要である
  • Author(s): 松本早紀子、桐生寿美子、木山博資
  • Organizer: 日本解剖学会
  • Place of Presentation: 自治医科大学（下野市）