Role of MITOL in mitochondrial function and oxidative stress signaling

2012 Fiscal Year Final Research Report

• Project/Area Number: 23650195
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: YANAGI Shigeru 東京薬科大学, 生命科学部, 教授 (60252003)
• Project Period (FY): 2011 – 2012
• Keywords: ミトコンドリア / ユビキチンリガーゼ / 酸化ストレス

Research Abstract

We previously identified a novel mitochondrial ubiquitin ligase called MITOL. MITOL has been shown to control mitochondrial dynamics by regulating mitochondrial fission factors such as Drp1 (EMBO J 2006). In this research project, we found that MITOL protects neuronal cells from mitochondrial damage caused by accumulation of MAP1B-light chain 1 (PNAS 2012). Therefore, MITOL is involved in mitochondrial dynamics, mitochondrial quality control, and protection against oxidative stress. Most recently, we foundthat MITOL regulates E R-mitochondria interaction by controlling Mfn2 activity (Mol Cell 2013). These results suggest that MITOL plays a critical role in mitochondrial regulation and oxidative signaling. Further investigations may shed light on new protective role of MITOL against oxidative stresses

Research Products

• [Journal Article] MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. (2013)
  • Author(s): Sugiura, A., Nagashima, S., Tokuyama, T., Amo, T., Matsuki, Y., Ishido, S., Kudo, Y., McBride, H.M., Fukuda, T., Matsushita, T., Inatome, R., and C Yanagi, S.
  • Journal Title: Mol. Cell Volume: 51 Pages: 1-15
  • DOI: DOI:10.1016/j.molcel 2013.04.023
• [Journal Article] Mitochondrial ubiquitin ligase MITOL blocks S-nitrosylated MAP1B-light chain 1-mediated mitochondrial dysfunction and neuronal cell death (2012)
  • Author(s): Yonashiro, R., Kimijima, Y., Shimura, T., Kawaguchi, K., Fukuda, T., Inatome, R., and Yanagi, S.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 109(7) Pages: 2382-2387
  • DOI: DOI:10.1073/pnas.1114985109
• [Journal Article] CRAG protects neuronal cells against cytotoxicity of expanded polyglutamine protein partially via c-fos-dependent AP-1 activation (2011)
  • Author(s): Nagashima, S., Fukuda, T., Kubota, Y., Sugiura, A., Nakao, M., Inatome, R., and Yanagi, S
  • Journal Title: J. Biol. Chem Volume: 286(39) Pages: 33879-33889
  • DOI: DOI:10.1074/jbc.M111.234997
• [Journal Article] DirectInhibiton of TNF-a promoter activity by Fanconi anemia (2011)
  • Author(s): Matsushita, N., Endo, Y., Sato, K., Kurumizaka, H., Yamashita, T., Takata, M., and Yanagi, S
  • Journal Title: PLoS ONE Volume: 6(8) Pages: e23324
  • DOI: DOI:10.1371/journal.pone.0023324
• [Presentation] ミトコンドリアユビキチンリガーゼMITOLの機能解析 (2012)
  • Author(s): 杉浦 歩、與那城亮、長島 駿、柳 茂
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] MITOL欠損が及ぼす細胞内への影響の解析 (2012)
  • Author(s): 吉田有里,徳山剛士, 稲留涼子, 長島 駿, 石戸 聡, 柳 茂
  • Organizer: 第86回日本生化学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] CAMDI遺伝子ノックアウトマウスにおける大脳皮質の解析 (2012)
  • Author(s): 山崎紘子、福田敏史、柳 茂
  • Organizer: 第86回日本生化学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-15
• [Presentation] A critical role of CRAG in neuronal cell survival and possible use of CRAG as a gene therapy for neurodegenerative diseases (2012)
  • Author(s): Yanagi, S
  • Organizer: The 11th biennial meeting of Asian Pacific Society for Neurochemistry (APSN), the 55th Meeting of Japanese Society for Neurochemistry (JSN)
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2012-10-02
• [Presentation] ミトコンドリアユビキチンリガーゼMITOL によるミトコンドリア機能調節と神経疾患 A role of mitochondrial ubiquitin ligas MITOL in mitochondrial function and neurological disorder Neuro2012 (2012)
  • Author(s): 柳 茂
  • Organizer: 第35回日本神経科学大会 シンポジウム「神経系のミトコンドリア疾患学」
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-20
• [Presentation] ファンコニ貧血蛋白FANCD2 によるNF-kappaB 転写制御機構の解析FANCD2 regulates NF-kappaB transcriptional activity (2011)
  • Author(s): 松下暢子、菊間啓太、太田莉英子、〓龍介、徳山剛士、高田穣、胡桃坂仁志、山下孝之、稲留涼子、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Analysis of the Fanconi Anemia pathway (2011)
  • Author(s): 菊間啓太、松下暢子、志村卓哉、川口浩平、吉田有里、加藤翔、稲留涼子、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] ミトコンドリアユビキチンリガーゼ、MITOL のS-ニトロシル化による活性制御機構の解析Regulation of ubiquitin ligase activity of MITOL by S-nitrosylation (2011)
  • Author(s): 志村卓哉、與那城亮、川口浩平、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] ミトコンドリアユビキチンリガーゼ、MITOL の基質認識機構の解析.Analysis of substrate recognition of MITOL (2011)
  • Author(s): 川口浩平、志村卓哉、加藤翔太、吉田有里、與那城亮、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] TAX1BP1 欠損DT40 細胞の機能解析～NF-κB 転写活性亢進が細胞に与える影響の検討～Functional Analysis ofTAX1BP1 deficient cells (2011)
  • Author(s): 太田莉英子、松下暢子、〓龍介、徳山剛士、稲留涼子、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Functional Analysis of CAMDI during hippocampus development (2011)
  • Author(s): 服部晶、福田敏史、岩瀬彩香、須田幸司、三浦恒平、山崎紘子、渡部愛美、長島駿、稲留涼子、柳茂
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] 統合失調症脆弱遺伝子DISC1に関連する新規遺伝子CAMDIの機能解析 (2011)
  • Author(s): 柳茂
  • Organizer: 第38回日本脳科学会
  • Place of Presentation: 那覇
  • Year and Date: 2011-10-08
• [Presentation] S-ニトロ化MAP1B-LC1 によるミトコンドリア機能不全とMITOL による防御機構 (2011)
  • Author(s): 柳茂、杉浦歩、與那城亮
  • Organizer: 第84回日本生化学会大会シンポジウム「疾患に関与するミトコンドリア研究の新展開」
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] ミトコンドリアユビキチンリガーゼの機能解析と神経変性疾患 (2011)
  • Author(s): 柳茂
  • Organizer: 厚生労働科学研究費補助金(難治性疾患克服研究事業)「神経変性疾患に関する調査研究班」の分科班「病態に根ざしたALSの新規治療法開発班」平成23年度ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2011-09-22
• [Presentation] CRAG はc-fos 依存的なAP-1 の活性化を介して異常伸長したポリグルタミンの毒性から細胞を保護する CRAG protects neuronal cells against cytotoxicity of expanded polyglutamine protein partially via c-fos-dependent AP-1 activation (2011)
  • Author(s): 長島 駿、福田敏史、岩瀬彩香、三浦恒平、稲留涼子、柳 茂
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] Functional regulation of Mfn2 by mitochondrial ubiquitin ligase MITOL (2011)
  • Author(s): Sugiura, A., Yanagi, S.
  • Organizer: Mitochondrial Dynamics: from Mechanism to Disease
  • Place of Presentation: Sardinia, Italy
  • Year and Date: 2011-09-12
• [Presentation] Role of Mitochondrial Ubiquitin Ligase MITOL in Mitochondrial Function (2011)
  • Author(s): Yanagi, S., Sugiura, A., Inatome, R., Yonashiro, R
  • Organizer: 5th Biennial Meeting of Society for Free Radical Research-Asia(SFRR-Asia), 8th Conference of Asian Society for Mitochondrial Research and Medicine(ASMRM), 11th Conference of Japanese Society of Mitochondrial Research and Medicine(J-mit)
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2011-09-02