Investigation and physiological analysis of the quantity control factor of mitochondrial DNA

• Project/Area Number: 22680035
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: 公益財団法人東京都医学総合研究所 (2012); Tokyo Metropolitan Organization for Medical Research (2010-2011)
• Principal Investigator: SHITARA Hiroshi 公益財団法人東京都医学総合研究所, 基盤技術研究センター, 基盤技術研究職員 (90321885)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000); Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2010: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
• Keywords: 遺伝学 / ミトコンドリア / ミトコンドリアDNA / ミトコンドリアDNA量

Research Abstract

Mitochondrial DNA (mtDNA) in mammalian cells exists as multiple copies, which are regulated by various genetic and environmental factors. In this study, we analyzed the regulatory effect of mitochondrial transcription factor A (Tfam) and observed that its overexpression improves the symptoms of mitochondrial deficiency in a mouse model.

Research Products

• [Journal Article] Mitochondrial physiology and gene expression analyses reveal metabolic and translational dysregulation in oocyte-induced somatic nuclear reprogramming (2012)
  • Author(s): T. C. Esteves, O. E. Psathak, M. J. Pfeiffer, S. T. Balbach, D. Zeuschner, H. Shitara, H. Yonekawa, M. Boiani
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e36850-e36850
  • DOI: 10.1371/journal.pone.0036850
  • Peer Reviewed
• [Journal Article] Comprehensive application of an mtDsRed2-Tg mouse strain for mitochondrial imaging (2012)
  • Author(s): Yamaguchi, J., Nishiyama, S., Shimanuki, M., Ono, T., Sato, A., Nakada, K., Hayashi, J-I., Yonekawa, H., Shitara, H
  • Journal Title: Transgenic Research Volume: 21巻 Issue: 2 Pages: 439-447
  • DOI: 10.1007/s11248-011-9539-1
  • Peer Reviewed
• [Journal Article] マウスにおけるmtDNA遺伝様式:母性遺伝と急調分離 (2011)
  • Author(s): 設楽浩志、米川博通
  • Journal Title: Plant Morphology Volume: 23 Pages: 35-40
  • NAID: 130002152897
• [Journal Article] 哺乳動物におけるミトコンドリアDNAの遺伝様式:急調分離とボトルネック効果 (2011)
  • Author(s): 設楽浩志
  • Journal Title: 細胞工学 Volume: 29 Pages: 461-465
• [Journal Article] p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria (2011)
  • Author(s): Kei Okatsu
  • Journal Title: Genes to Cells Volume: 15 Pages: 887-900
  • Peer Reviewed
• [Journal Article] Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells (2011)
  • Author(s): Mutsumi Yokota, Hiroshi Shitara (equal contribution)
  • Journal Title: FEBS Letters Volume: 584 Pages: 3943-3948
  • NAID: 120007137913
  • Peer Reviewed
• [Journal Article] Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse model system (2011)
  • Author(s): Satoshi Nishiyama, Hiroshi Shitara (equal contribution)
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 401 Pages: 26-31
  • NAID: 120007137866
  • Peer Reviewed
• [Journal Article] Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse model system (2010)
  • Author(s): Nishiyama, S., Shitara, H., Nakada, K., Ono, T., Sato, A., Suzuki, H., Ogawa, T., Masaki, H., Hayashi, J-I., Yonekawa, H
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 401巻 Issue: 1 Pages: 26-31
  • DOI: 10.1016/j.bbrc.2010.08.143
  • NAID: 120007137866
  • Peer Reviewed
• [Journal Article] Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells (2010)
  • Author(s): Yokota, M., Shitara, H., Hashizume, O., Ishikawa, K., Nakada, K., Ishii, R., Taya, C., Takenaga, K., Yonekawa, H., Hayashi, J
  • Journal Title: FEBS letters Volume: 584巻 Issue: 18 Pages: 3943-3948
  • DOI: 10.1016/j.febslet.2010.07.048
  • NAID: 120007137913
  • Peer Reviewed
• [Journal Article] 哺乳動物におけるミトコンドリアDNAの遺伝様式:急調分離とボトルネック効果 (2010)
  • Author(s): 設楽浩志、曹麗琴、米川博通
  • Journal Title: 細胞工学 Volume: 29 Pages: 461-465
• [Presentation] マウス組織におけるミトコンドリアDNA量の相対定量解析 (2012)
  • Author(s): 島貫碧
  • Organizer: 日本ミトコンドリア学会第12回年会
  • Place of Presentation: つくば
• [Presentation] マウス組織におけるmtDNA量およびミトコンドリアの転写と複製に関わる遺伝子群の発現量解析 (2012)
  • Author(s): 島貫碧
  • Organizer: 第59日本実験動物学会総会
  • Place of Presentation: 大分
• [Presentation] Tfam/EGFP過剰発現マウスにおける異質性ミトコンドリアDNA分離様式の解析 (2012)
  • Author(s): 山口潤也
  • Organizer: 第59日本実験動物学会総会
  • Place of Presentation: 大分
• [Presentation] Tfam/EGFP過剰発現マウスにおける異質性ミトコンドリアDNA分離様式の解析 (2012)
  • Author(s): 山口潤也
  • Organizer: 第５９日本実験動物学会総会
  • Place of Presentation: 大分
• [Presentation] マウス組織におけるmtDNA量およびミトコンドリアの転写と複製に関わる遺伝子群の発現量解析 (2012)
  • Author(s): 島貫碧
  • Organizer: 第５９日本実験動物学会総会
  • Place of Presentation: 大分
• [Presentation] マウス組織におけるミトコンドリアDNA量の相対定量解析 (2012)
  • Author(s): 島貫碧
  • Organizer: 日本ミトコンドリア学会第１２回年会
  • Place of Presentation: つくば
• [Presentation] ミトコンドリア転写因子A過剰発現によるミトコンドリア機能低下の抑制効果 (2011)
  • Author(s): 設楽浩志
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)(招待講演)
  • Year and Date: 2011-09-21
• [Presentation] 新規ミトコンドリア標的抗酸化剤の開発とモデルマウスを用いた薬理効果の検討 (2011)
  • Author(s): 坂井隆浩
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2011-05-25
• [Presentation] ミトコンドリア形態解析法としてのmtDsRed2-Tg系統の有用性 (2011)
  • Author(s): 山口潤也
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2011-05-25
• [Presentation] マウスモデルを用いたTfam過剰発現によるミトコンドリア機能低下の抑制効果の解析 (2011)
  • Author(s): 設楽浩志
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2011-05-25
• [Presentation] ミトコンドリア転写因子A過剰発現によるミトコンドリア機能低下の抑制効果 (2011)
  • Author(s): 設楽浩志
  • Organizer: 第84回日本生化学会大会(シンポジウム)
  • Place of Presentation: 京都
• [Presentation] mtDsRed2 transgenic mice contribute to studies on mitochondrial morphology (2011)
  • Author(s): J. Yamaguchi
  • 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
• [Presentation] Tfam過剰発現によるミトコンドリア疾患の発症抑制効果モデル (2011)
  • Author(s): 設楽浩志
  • Organizer: 第25回モロシヌス研究会
  • Place of Presentation: 新潟
• [Presentation] mtDsRed2-Tg系統を用いたミトコンドリア形態解析 (2011)
  • Author(s): 山口潤也
  • Organizer: 第25回モロシヌス研究会
  • Place of Presentation: 新潟
• [Presentation] Mouse strain mtDsRed2-Tg strain: A powerful tool for mitochondrial imaging (2011)
  • Author(s): J. Yamaguchi
  • Organizer: The 8th European Meeting on Mitochondrial Pathology (Euromit 8)
  • Place of Presentation: Zaragoza, Spain
• [Presentation] Over-expression of mitochondrial transcription factor A prevents effectively the onset of mitochondrial disease in a mouse model system (2011)
  • Author(s): H. Shitara
  • Organizer: The 8th European Meeting on Mitochondrial Pathology (Euromit 8)
  • Place of Presentation: Zaragoza, Spain
• [Presentation] C57BL/6J-mtsprコンプラスティック系統における組織mtDNA量の相対定量解析 (2011)
  • Author(s): 島貫碧
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: 東京
• [Presentation] マウスモデルを用いたTfam過剰発現によるミトコンドリア機能低下の抑制効果の解析 (2011)
  • Author(s): 設楽浩志
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: 東京
• [Presentation] ミトコンドリア形態解析法としてのmtDsRed2-Tg系統の有用性 (2011)
  • Author(s): 山口潤也
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: 東京
• [Presentation] C57BL/6J-mtsprコンプラスティック系統における組織mtDNA量の相対定量解析 (2011)
  • Author(s): 島貫碧
  • Organizer: 第58日本実験動物学会総会
  • Place of Presentation: タワーホール船堀(東京都)
• [Presentation] Over-expression of mitochondrial transcription factor A prevents effectively the onset of mitochondrial disease in a mouse model system (2011)
  • Author(s): Hiroshi Shitara
  • Organizer: The 8th European Meeting on Mitochondrial Pathology (Euromit 8)
  • Place of Presentation: Zaragoza (Spain)
• [Presentation] Mouse strain mtDsRed2-Tg strain : A powerful tool for mitochondrial imaging (2011)
  • Author(s): Junya Yamaguchi
  • Organizer: The 8th European Meeting on Mitochondrial Pathology (Euromit 8)
  • Place of Presentation: Zaragoza (Spain)
• [Presentation] Tfam過剰発現によるミトコンドリア疾患の発症抑制効果モデル (2011)
  • Author(s): 設楽浩志
  • Organizer: 第25回モロシヌス研究会
  • Place of Presentation: ベルナティオ(新潟県)
• [Presentation] mtDsRed2-Tg系統を用いたミトコンドリア形態解析 (2011)
  • Author(s): 山口潤也
  • Organizer: 第25回モロシヌス研究会
  • Place of Presentation: ベルナティオ(新潟県)
• [Presentation] mtDsRed2 transgenic mice contribute to studies on mitochondrial morphology (2011)
  • Author(s): Junya Yamaguchi
  • Organizer: 5th SFRR-Asia & 8th ASMRM & 11th J-Mit
  • Place of Presentation: 鹿児島市民文化ホール(鹿児島)
• [Presentation] Therapeutic effect of Tfam over-expression in a mouse model of mitochondrial disease (2011)
  • Author(s): Hiroshi Shitara
  • Organizer: The 10th Transgenic Technology Meeting (TT2011)
  • Place of Presentation: Florida (USA)
• [Presentation] Characterization of mitochondrial morphology in various tissues of and primary adherent cells from transgenic mice expressing mitochondrially (2011)
  • Author(s): Midori Shimanuki
  • Organizer: The 10th Transgenic Technology Meeting (TT2011)
  • Place of Presentation: Florida (USA)
• [Presentation] Mitochondrial imaging of in tissues by using mtDsRed2-Tg mouse strain (2011)
  • Author(s): Junya Yamaguchi
  • Organizer: The 10th Transgenic Technology Meeting (TT2011)
  • Place of Presentation: Florida (USA)
• [Presentation] Mitochondrial Disease Therapy by Tfam Over-expression in a Mouse Model System (2010)
  • Author(s): S. Nishiyama
  • Organizer: Asian Society for Mitochondrial Research and Medicine (7th ASMRM) and Japanese Society of Mitochondrial Research and Medicine (10th J-mit)
  • Place of Presentation: Fukuoka
• [Presentation] マウスにおけるmtDNA遺伝様式 (2010)
  • Author(s): 設楽浩志
  • Organizer: 日本植物学会第74回大会(シンポジウム)
  • Place of Presentation: 春日井
• [Presentation] ミトコンドリアボトルネック効果はmtDNAコピー数の減少が原因ではないことの新たな証拠 (2010)
  • Author(s): 設楽浩志
  • Organizer: 第57日本実験動物学会総会
  • Place of Presentation: 京都
• [Presentation] マウスにおけるmtDNA遺伝様式 (2010)
  • Author(s): 設楽浩志
  • Organizer: 日本植物学会第74回大会
  • Place of Presentation: 春日井(愛知県)(招待講演)
• [Presentation] Mitochondrial Disease Therapy by Tfam Over-expression in a Mouse Model System (2010)
  • Author(s): Satoshi Nishiyama
  • Organizer: Asian Society for Mitochondrial Research and Medicine (7th ASMRM) and Japanese Society of Mitochondrial Research and Medicine (10th J-mit)
  • Place of Presentation: Fukuoka, Japan
• [Book] 外来性ミトコンドリア導入によるミトコンドリアDNAヘテロプラズミーマウス系統の樹立、生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 設楽浩志
  • Publisher: エル・アイ・シー
• [Book] 卵子ミトコンドリアDNA、卵子学 (2011)
  • Author(s): 林純一,設楽浩志,佐藤晃嗣
  • Publisher: 京都大学学術出版会
• [Book] 卵子学 (2011)
  • Author(s): 林純一
  • Publisher: 京都大学学術出版会
• [Book] 生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 設楽浩志
  • Publisher: (株)エル・アイ・シー