Mitochondrial dysfunction by loss of CHCHD2.

• Project/Area Number: 17K09769
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• 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学群), 応用科学群, 准教授 (40453922)
• Co-Investigator(Kenkyū-buntansha): 竹清 貴浩 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 (00545981)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミトコンドリア / パーキンソン病 / α-シヌクレイン

Outline of Final Research Achievements

Mitochondrial dysfunction is a hallmark of Parkinson's disease. In this study, we showed mitochondrial dysfunction caused by loss of CHCHD2. We also revealed comprehensive metabolic disturbances including mitochondrial dysfunction in a cellular model of Parkinson’s disease. Further, we investigated the anti-amyloid effect of ethylammonium salts in vitro.

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やα-シヌクレイン凝集に端を発するレビー小体形成が重要であると考えられる。本研究の成果は、パーキンソン病の病態解明、ミトコンドリアやα-シヌクレイン凝集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] 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] 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] 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] 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
• [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] Aggregation selectivity of amyloid β1‐11 peptide in aqueous ionic liquid solutions (2020)
  • Author(s): Takekiyo Takahiro、Yamada Natsuki、Amo Taku、Yoshimura Yukihiro
  • Journal Title: Peptide Science Volume: 112 Issue: 2
  • DOI: 10.1002/pep2.24138
  • Peer Reviewed
• [Journal Article] Metabolomic analysis revealed mitochondrial dysfunction and aberrant choline metabolism in MPP+-exposed SH-SY5Y cells (2019)
  • Author(s): Amo Taku、Oji Yutaka、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 519 Issue: 3 Pages: 540-546
  • DOI: 10.1016/j.bbrc.2019.09.031
  • Peer Reviewed
• [Journal Article] Mitochondrial Remodeling in Endothelial Cells under Cyclic Stretch is Independent of Drp1 Activation (2019)
  • Author(s): Baba Megumi、Shinmura Aya、Tada Shigeru、Amo Taku、Tsukamoto Akira
  • Journal Title: Molecular & Cellular Biomechanics Volume: 16 Issue: 1 Pages: 1-12
  • DOI: 10.32604/mcb.2019.05199
  • Peer Reviewed / Open Access
• [Journal Article] Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions (2019)
  • Author(s): Fujimaki Motoki、Furuya Norihiko、Saiki Shinji、Amo Taku、Imamichi Yoko、Hattori Nobutaka
  • Journal Title: Molecular and Cellular Biology Volume: 39 Issue: 14
  • DOI: 10.1128/mcb.00010-19
  • Peer Reviewed / Open Access
• [Journal Article] Cooling Effect on Amyloid Aggregates (2019)
  • Author(s): 竹清 貴浩、武川 裕大、山田 菜月、天羽 拓、吉村 幸浩
  • Journal Title: Cryobiology and Cryotechnology Volume: 65 Issue: 2 Pages: 63-66
  • DOI: 10.20585/cryobolcryotechnol.65.2_63
  • NAID: 130007782649
  • ISSN: 1340-7902, 2424-1555
  • Peer Reviewed
• [Journal Article] Characterization of Mitochondrial Content and Respiratory Capacities of Broiler Chicken Skeletal Muscles with Different Muscle Fiber Compositions (2018)
  • Author(s): 1.Hakamata, Y., Watanabe, K., Amo, T., Toyomizu, M. and Kikusato, M.
  • Journal Title: The Journal of Poultry Science Volume: 55 Issue: 3 Pages: 210-216
  • DOI: 10.2141/jpsa.0170141
  • NAID: 130007419002
  • ISSN: 1346-7395, 1349-0486
  • Peer Reviewed / Open Access
• [Journal Article] Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184-16193 poly-cytosine tract), which confer resistance to cisplatin. (2017)
  • Author(s): Amo T, Kamimura N, Asano H, Asoh S, Ohta S.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46240-46240
  • DOI: 10.1038/srep46240
  • Peer Reviewed / Open Access
• [Journal Article] Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson's disease. (2017)
  • Author(s): Saiki S, Hatano T, Fujimaki M, Ishikawa K, Mori A, Oji Y, Okuzumi A, Fukuhara T, Koinuma T, Nagumo M, Furuya N, Nojiri S, Amo T, Yamashiro K, Hattori N.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 7328-7328
  • DOI: 10.1038/s41598-017-06767-y
  • Peer Reviewed / Open Access
• [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
• [Presentation] アミロイド凝集体に及ぼす冷却効果 (2019)
  • Author(s): 竹清 貴浩、武川 裕大、山田 菜月、天羽 拓、吉村 幸浩
  • Organizer: 第64回 低温生物工学会大会
• [Presentation] パーキンソン病関連疾患鑑別における脂肪酸β酸化変化のバイオマーカーとしての有効 (2019)
  • Author(s): 竹重 遥香、斉木 臣二、藤巻 基紀、波田野 琢、石川 景一、森 聡生、王子 悠、奥住 文美、濃沼 崇博、上野 真一、今道 洋子、野尻 宗子、天羽 拓、服部 信孝
  • Organizer: 第13回 パーキンソン病・運動障害疾患コングレス
• [Presentation] 肉用鶏と産卵鶏のミトコンドリア呼吸鎖複合体超複合体(SCs)形成量およびエネルギー代 謝特性の違い (2019)
  • Author(s): 袴田 祐基、天羽 拓、豊水 正昭、喜久里 基
  • Organizer: 日本畜産学会 第126回大会
• [Presentation] イオン液体を用いたα-シヌクレインアミロイド形成の制御 (2019)
  • Author(s): 山田 菜月、天羽 拓、竹清 貴浩、吉村 幸浩
  • Organizer: 第42回 溶液化学シンポジウム
• [Presentation] イオン液体水溶液中のAmyloid β1-11ペプチドの凝集選択性 (2019)
  • Author(s): 竹清 貴浩、山田 菜月、天羽 拓、吉村 幸浩
  • Organizer: 第42回 溶液化学シンポジウム
• [Presentation] エチルアンモニウム系イオン液体を用いたα-synucleinのアミロイド凝集選択性 (2019)
  • Author(s): 山田 菜月、天羽 拓、竹清 貴浩、吉村 幸浩
  • Organizer: 第10回 イオン液体討論会
• [Presentation] CHCHD2 deficiency leads to mitochondrial dysfunction in human neuroblastoma SY-SY5Y cells. (2018)
  • Author(s): T.Amo, M.Funayama, J.S.Park, N.Furuya, S.Saiki, W.Akamatsu, C.M.Sue, N.Hattori
  • Organizer: Keystone Symposia, Mitochondrial Biology
  • Int'l Joint Research
• [Presentation] Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184-16193 poly-cytosine tract), which confer resistance to cisplatin (2017)
  • Author(s): Amo T, Kamimura N, Asano H, Asoh S, Ohta S
  • Organizer: Euromit 2017 (International meeting on mitochondrial pathology)
  • Int'l Joint Research
• [Presentation] CHCHD2 deficiency leads to mitochondrial dysfunction and increasing oxidative stress in human neuroblastoma SH-SY5Y cells (2017)
  • Author(s): Funayama M, Park JS, Amo T, Funayama T, Akamatsu W, Sue CM, Hattori N
  • Organizer: XXIII World Congress of Neurology (WCN 2017)
  • Int'l Joint Research