Mitochondrial dysfunction in familial Parkinson's disease.

• Project/Area Number: 24790903
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: 防衛大学校(総合教育学群、人文社会科学群、応用科学群、電気情報学群及びシステム工学群)
• Principal Investigator: AMO Taku 防衛大学校(総合教育学群、人文社会科学群、応用科学群、電気情報学群及びシステム工, 応用科学群, 助教 (40453922)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: パーキンソン病 / ミトコンドリア

Outline of Final Research Achievements

Mitochondrial dysfunction is a hallmark of both idiopathic and familial Parkinson's disease (PD). In this study, detailed analysis of mitochondrial dysfunction caused by loss of PINK1 revealed both of mitochondrial Complex I and III deficiencies. Recently, CHCHD2 was identified as a novel causative gene in mendelian forms of Parkinson’s disease. In this study, it was shown that CHCHD2 was localized in mitochondrial intermembrane space.

Research Products

• [Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. (2015)
  • Author(s): Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
  • Journal Title: Lancet Neurol Volume: 14 Issue: 3 Pages: 274-282
  • DOI: 10.1016/s1474-4422(14)70266-2
  • Peer Reviewed / Open Access
• [Journal Article] Detailed analysis ofmitochondrial respiratory chain defects caused by loss of PINK1. (2014)
  • Author(s): Amo T, Saiki S, Sawayama T, Sato S, Hattori N.
  • Journal Title: Neurosci Lett. Volume: 580 Pages: 37-40
  • DOI: 10.1016/j.neulet.2014.07.045
  • Peer Reviewed
• [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 Issue: 1 Pages: 1-15
  • DOI: 10.1016/j.molcel.2013.04.023
  • Peer Reviewed
• [Journal Article] A mitochondrial ubiquitin ligase MITOL regulates endoplasmic reticulum-mitochondria interaction via mitofusin2 (2013)
  • Author(s): A. Sugiura, S. Nagashima, T. Tokuyama, T. Amo, Y. Matsuki, S. Ishido, Y. Kudo, H. M. McBride, T. Fukuda, N. Matsushita, R. Inatome, S. Yanagi
  • Journal Title: Molecular Cell
  • Peer Reviewed
• [Presentation] 寒冷曝露下の鶏における骨格筋FNDC5/Irisin発現と脂肪組織avUCP発現の連関 (2015)
  • Author(s): 栗谷川あんな, 喜久里基, 白川仁, 天羽拓, 豊水正昭
  • Organizer: 第119回日本畜産学会大会
  • Place of Presentation: 宇都宮大学峰キャンパス（栃木県宇都宮市）
  • Year and Date: 2015-03-27 – 2015-03-30
• [Presentation] 常染色体優性遺伝性パーキンソン病の新規原因遺伝子単離 (2015)
  • Author(s): 舩山学, 大江賢治, 天羽拓, 古屋徳彦, 山口隼司, 斉木臣二, 李元哲, 大垣光太郎, 安藤真矢, 吉野浩代, 富山弘幸, 西岡健弥, 長谷川一子, 斎木英資, 佐竹渉, 茂櫛薫, 佐々木良元, 小久保康昌, 葛原茂樹, 戸田達史, 水野美邦, 内山安男, 大野欽司, 服部信孝
  • Organizer: 第49回日本運動障害研究会
  • Place of Presentation: 大日本住友製薬（株）東京本社（東京都中央区）
  • Year and Date: 2015-01-17
• [Presentation] 抗がん剤感受性を悪化させるミトコンドリアDNAのD-loop領域変異 (2014)
  • Author(s): 天羽拓, 宮本哲也, 上村尚美, 浅野弘匡, 麻生定光, 太田成男
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 抗がん剤感受性を悪化させるミトコンドリアDNAのD-loop領域変異 (2014)
  • Author(s): 天羽拓, 宮本哲也, 上村尚美, 浅野弘匡, 麻生定光, 太田成男
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] A somatic mutation of mitochondrial DNA confers resistance against an anti-cancer drug. (2014)
  • Author(s): Taku Amo, Tetsuya Miyamoto, Naomi Kamimura, Sadamitsu Asoh and Shigeo Ohta
  • Organizer: 9th International Meeting on Mitochondrial Pathology (Euromit2014)
  • Place of Presentation: Tampere (Finland)
  • Year and Date: 2014-06-15 – 2014-06-19
• [Presentation] PINK1,parkin過剰発現による細胞保護的なmitophagyの亢進がapoptosisを 誘導する (2014)
  • Author(s): 河村美巴子，斉木臣二，古屋徳彦，今道洋子，天羽拓，矢野浩二郎， 服部信孝
  • Organizer: 第55 回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] ピロロキノリンキノン(PQQ)の添加が単離鶏ミトコンドリアの呼吸機能に及ぼす影響 (2014)
  • Author(s): 田邉拓也, 喜久里基, 天羽拓, 豊水正昭
  • Organizer: 日本畜産学会 第118回大会
  • Place of Presentation: つくば国際会議場（茨城県）
• [Presentation] PINK1/parkin 過剰発現によるmitophagyとapoptosisの誘導作用について (2013)
  • Author(s): 河村美巴子, 斉木臣二, 古屋徳彦, 今道洋子, 天羽拓, 矢野浩二朗, 服部信孝
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京都）
• [Presentation] Detailed analyses of mitochondrial respiratory chain defects caused by loss of PINK1 (2013)
  • Author(s): T. Amo, T. Sawayama, S. Sato, S. Saiki, A. M. Wolf, M. Toyomizu, T. Ichimura, C. A. Gautier, J. Shen, S. Ohta, N. Hattori
  • Organizer: The 4th International Symposium on Dynamics of Mitochondria (DynaMito2013)
  • Place of Presentation: 沖縄残波岬ロイヤルホテル（沖縄県）
• [Presentation] A somatic mutation of mitochondrial DNA confers resistance against an anti-cancer drug (2013)
  • Author(s): T. Amo, T. Miyamoto, N. Kamimura, S. Asoh, S. Ohta
  • Organizer: International Symposium on Mitochondria 2013
  • Place of Presentation: 六本木アカデミーヒルズ49（東京都）
• [Presentation] 家族性パーキンソン病原因遺伝子PINK1欠損によるミトコンドリア膜電位低下は プロトンリークではなく呼吸鎖機能低下のためである (2012)
  • Author(s): 天羽拓
  • Organizer: 認知症研究を知る若手研究者の集まり（主催：日本認知症学会）
  • Place of Presentation: あいち健康プラザ（愛知県）
• [Presentation] Mitochondrial Membrane Potential Decrease Caused by Loss of Pink1 is not Due to Proton Leak, but to Respiratory Chain Defects (2012)
  • Author(s): T.Amo, S.Sato, S.Saiki, A.M.Wolf, M.Toyomizu, C.A.Gautier, J.Shen, S.Ohta, N.Hattori
  • Organizer: European Bioenergetics Conference 2012
  • Place of Presentation: University of Freiburg (Germany)
• [Presentation] Excess of PINK1/parkin-mediated mitophagy induces apoptosis via various caspases activation (2012)
  • Author(s): M.Kawamura, S.Saiki, N.Furuya, Y.Imamichi, T.Amo, K.Yano, N.Hattori
  • Organizer: 6th International Symposium on Autophagy
  • Place of Presentation: 万国津梁館（沖縄県）