Mitochondrial dysfunction by loss of CHCHD8

• Project/Area Number: 20K07878
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• 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学群), 応用科学群, 准教授 (40453922)
• Co-Investigator(Kenkyū-buntansha): 舩山 学 順天堂大学, 医学部, 先任准教授 (70468578)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ミトコンドリア / パーキンソン病

Outline of Research at the Start

パーキンソン病発症機序としてミトコンドリア機能異常によるドパミン神経細胞死を示唆する知見が蓄積されており、その一つとして遺伝性パーキンソン病 (PARK22) の新規原因遺伝子産物CHCHD2がミトコンドリア膜間腔に局在することを示した。本研究ではCHCHD2欠損SH-SY5Y細胞などを用いて、ミトコンドリア機能障害に着目した分子機序を検討し、パーキンソン病でドパミン神経細胞特異的に変性が起こる原因に迫る。

Outline of Final Research Achievements

Mitochondrial dysfunction is a hallmark of Parkinson's disease. To gain insight into the molecular pathogenesis of Parkinson's disease, we analyzed CHCHD8, which has been identified as a factor associated with the Parkinson's disease causative gene product CHCHD2. CHCHD8-deficient human neuroblastoma SH-SY5Y showed significantly reduced respiratory chain complex IV activity. Based on decreased mitochondrial copper content and other factors, it was suggested that CHCHD8 is involved in the process of Cu delivery to the CuB center of the MTCO1 subunit.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病の発症機序は十分に解明されていないが、ミトコンドリア機能障害が重要なファクターであると考えられている。パーキンソン病原因遺伝子産物とミトコンドリア機能障害との関係の一端を明らかにした本研究の成果は、パーキンソン病の病態解明およびミトコンドリアを標的にした新規治療薬開発への貢献が期待される。

Research Products

• [Journal Article] Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort (2023)
  • Author(s): Vollstedt EJ, Schaake S, Lohmann K, Padmanabhan S, Brice A, Lesage S, Tesson C, Vidailhet M, Wurster I, Hentati F, Mirelman A, Giladi N, Marder K, Waters C, Fahn S, Kasten M, Bruggemann N, Borsche M, Foroud T, Tolosa E, Garrido A, Annesi G, Gagliardi M, Bozi M, Stefanis L, Ferreira JJ, Nishioka K, Funayama M, et. al.
  • Journal Title: Movement Disorders Volume: 38 Issue: 2 Pages: 286-303
  • DOI: 10.1002/mds.29288
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dissolution of amyloid aggregates by direct addition of alkali halides (2023)
  • Author(s): Takekiyo Takahiro、Yamada Natsuki、Amo Taku、Nakazawa Chikako T.、Asano Atushi、Ichimura Tohru、Kato Minoru、Yoshimura Yukihiro
  • Journal Title: Journal of Molecular Liquids Volume: 369 Pages: 120849-120849
  • DOI: 10.1016/j.molliq.2022.120849
  • Peer Reviewed
• [Journal Article] Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation (2022)
  • Author(s): Tokuyama T、Uosaki H、Sugiura A、Nishitai G、Takeda K、Nagashima S、Shiiba I、Ito N、Amo T、Mohri S、Nishimura A、Nishida M、Konno A、Hirai H、Ishido S、Yoshizawa T、Shindo T、Takada S、Kinugawa S、Inatome R、Yanagi S
  • Journal Title: iScience Volume: 25 Issue: 7 Pages: 104582-104582
  • DOI: 10.1016/j.isci.2022.104582
  • Peer Reviewed / Open Access
• [Journal Article] Deep Brain Stimulation for a Patient with Familial Parkinson's Disease Harboring CHCHD2 p.T61I. (2022)
  • Author(s): Kamo Hikaru、Oyama Genko、Nishioka Kenya、Funayama Manabu、Hattori Nobutaka
  • Journal Title: Movement Disorders Clinical Practice Volume: 9 Issue: 3 Pages: 407-409
  • DOI: 10.1002/mdc3.13428
  • Peer Reviewed / Open Access
• [Journal Article] Triiodide ion-induced inhibition of amyloid aggregate formation: A case study of α-synuclein (2022)
  • Author(s): Takekiyo Takahiro、Yamada Natsuki、Amo Taku、Asano Atsushi、Yoshimura Yukihiro
  • Journal Title: Journal of Molecular Liquids Volume: 360 Pages: 119446-119446
  • DOI: 10.1016/j.molliq.2022.119446
  • Peer Reviewed
• [Journal Article] Metabolomic analysis data of MPP+-exposed SH-SY5Y cells using CE-TOFMS (2021)
  • Author(s): Amo Taku、Oji Yutaka、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Data in Brief Volume: 34 Pages: 106707-106707
  • DOI: 10.1016/j.dib.2020.106707
  • Peer Reviewed / Open Access
• [Journal Article] Homeostatic p62 levels and inclusion body formation in CHCHD2 knockout mice (2021)
  • Author(s): Sato Shigeto、Noda Sachiko、Torii Satoru、Amo Taku、Ikeda Aya、Funayama Manabu、Yamaguchi Junji、Fukuda Takahiro、Kondo Hiromi、Tada Norihiro、Arakawa Satoko、Watanabe Masahiko、Uchiyama Yasuo、Shimizu Shigeomi、Hattori Nobutaka
  • Journal Title: Human Molecular Genetics Volume: 30 Issue: 6 Pages: 443-453
  • DOI: 10.1093/hmg/ddab057
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo emergence of beige-like fat in chickens as physiological adaptation to cold environments (2021)
  • Author(s): Sotome Rina、Hirasawa Akira、Kikusato Motoi、Amo Taku、Furukawa Kyohei、Kuriyagawa Anna、Watanabe Kouichi、Collin Anne、Shirakawa Hitoshi、Hirakawa Ryota、Tanitaka Yuta、Takahashi Hideki、Wu Guoyao、Nochi Tomonori、Shimmura Tsuyoshi、Warden Craig H.、Toyomizu Masaaki
  • Journal Title: Amino Acids Volume: 53 Issue: 3 Pages: 381-393
  • DOI: 10.1007/s00726-021-02953-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Formation of α‐synuclein aggregates in aqueous ethylammonium nitrate solutions (2020)
  • Author(s): Takekiyo Takahiro、Yamada Natsuki、Nakazawa Chikako T.、Amo Taku、Asano Atsushi、Yoshimura Yukihiro
  • Journal Title: Biopolymers Volume: 111 Issue: 6
  • DOI: 10.1002/bip.23352
  • Peer Reviewed
• [Journal Article] Effects of ethylammonium halides on helix formation of proteins (2020)
  • Author(s): Takekiyo Takahiro、Yamada Natsuki、Amo Taku、Yoshimura Yukihiro
  • Journal Title: Chemical Physics Letters Volume: 759 Pages: 137970-137970
  • DOI: 10.1016/j.cplett.2020.137970
  • Peer Reviewed
• [Presentation] Characterization of CHCHD2 variants linked to amyotrophic lateral sclerosis and Parkinson's disease (2023)
  • Author(s): A. Ikeda, M. Funayama, M. Yoshida, Y. Li, T. Inoshita, K. Shiba-Fukushima, H. Meng, T. Amo, I. Aiba, Y. Saito, N. Atsuta, R. Nakamura, G. Tohnai, J. Sone, Y. Izumi, R. Kaji, M. Morita, A. Taniguchi, K. Nishioka, Y. Imai, G. Sobue, N. Hattori, JaCALS
  • Organizer: 第64回日本神経学会学術大会
• [Presentation] Loss of CHCHD8 (COA4) caused mitochondrial respiratory Complex IV deficiency (2023)
  • Author(s): Taku Amo, Yuga Hikage
  • Organizer: Euromit 2023
  • Int'l Joint Research
• [Presentation] CHCHD8 (COA4) はミトコンドリア呼吸鎖複合体IVの銅中心形成に関わる会合因子である (2023)
  • Author(s): 天羽 拓, 日景 勇賀
  • Organizer: 第46回日本分子生物学会年会
• [Presentation] CHCHD8 (COA4) 欠損によるミトコンドリア呼吸鎖複合体IVの機能不全 (2022)
  • Author(s): 天羽拓、日景勇賀
  • Organizer: 第21回日本ミトコンドリア学会年会
• [Presentation] SH-SY5YにおけるCHCHD8欠損によるミトコンドリア呼吸鎖複合体IVの機能不全 (2021)
  • Author(s): 日景 勇賀, 永沼 陸, 古本 菜々子, 舩山 学, 服部 信孝, 天羽 拓
  • Organizer: 第44回 日本分子生物学会年会
• [Presentation] SH-SY5YにおけるCHCHD8欠損によるミトコンドリア呼吸鎖複合体IVの機能不全 (2021)
  • Author(s): 日景 勇賀, 永沼 陸, 古本 菜々子, 舩山 学, 服部 信孝, 天羽 拓
  • Organizer: 第20回 日本ミトコンドリア学会年会
• [Presentation] ヒト神経芽細胞腫SH-SY5YにおけるCHCHD8 (COA4) 欠損によるミトコンドリア呼吸鎖複合体IVの機能不全 (2021)
  • Author(s): 日景 勇賀, 永沼 陸, 古本 菜々子, 天羽 拓
  • Organizer: 日本ミトコンドリア学会 特別オンラインシンポジウム
• [Presentation] CHCHD8 (COA4) 欠損によるミトコンドリア呼吸鎖複合体IVの機能不全 (2020)
  • Author(s): 日景 勇賀, 永沼 陸, 古本 菜々子, 山田 雅巳, 天羽 拓
  • Organizer: 第43回 日本分子生物学会年会