Studies on tissue-specific dynamics of pathogenic mutant mitochondrial DNA in mice

2012 Fiscal Year Final Research Report

• Project/Area Number: 22650091
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: NAKADA Kazuto 筑波大学, 生命環境系, 教授 (80323244)
• Project Period (FY): 2010 – 2012
• Keywords: ミトコンドリア / ミトコンドリアDNA / 病原性突然変異 / ミトコンドリア呼吸機能異常 / エネルギー欠損 / ミトコンドリア病 / モデルマウス

Research Abstract

Our model mouse study clearly shows that a single deleted mtDNA was responsible for at least two distinct disease phenotypes at different ages and suggests that the level and dynamics of deleted mtDNA load in affected tissues would be important for the onset and transition of disease phenotypes.

Research Products

• [Journal Article] Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development (2013)
  • Author(s): Mito T, Kikkawa Y, Shimizu A, Hashizume O, Katada S, Imanishi H, Ota A, Kato Y, Nakada K, Hayashi J
  • Journal Title: PLoS One Volume: 8(2) Pages: e55789
  • DOI: doi:10.1371/journal.pone.0055789
  • Peer Reviewed
• [Journal Article] Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development (2012)
  • Author(s): Hashizume O, Shimizu A, Yokota M, Sugiyama A, Nakada K, Miyoshi H, Itami M, Ohira M, Nagase H, Takenaga K, Hayashi J.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 109(26) Pages: 10528-33
  • DOI: doi:10.1073/pnas.1202367109
  • 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, Yonekawa H, Shitara H
  • Journal Title: Transgenic Res Volume: 21(2) Pages: 439-47
  • DOI: doi:10.1007/s11248-011-9539-1
  • Peer Reviewed
• [Journal Article] Transmitochondrial mice as models for mitochondrial DNA-based diseases.Exp Anim (2011)
  • Author(s): Nakada K, Hayashi J
  • Journal Title: Exp Anim Volume: 60(5) Pages: 421-31
  • URL: http://dx.doi.org/10.1538/expanim.60.421
  • Peer Reviewed
• [Journal Article] Mitochondrial DNA mutations regulate metastasis of human breast cancer cells (2011)
  • Author(s): Imanishi H, Hattori K, Wada R, Ishikawa K, Fukuda S, Takenaga K, Nakada K, Hayashi J
  • Journal Title: PLoS One Volume: 6(8) Pages: e23401
  • DOI: doi:10.1371/journal.pone.0023401
  • Peer Reviewed
• [Journal Article] Nuclear but not mitochondrial DNA involvement in respiratory complex I defects found in senescence-accelerated mouse strain (2011)
  • Author(s): Imanishi H, Yokota M, Mori M, Shimizu A, Nakada K, Hayashi J
  • Journal Title: SAMP8.Exp Anim Volume: 60(4) Pages: 397-404
  • URL: http://dx.doi.org/10.1538/expanim.60.397
  • Peer Reviewed
• [Journal Article] Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells (2011)
  • Author(s): Inami Y, Waguri S, Sakamoto A, Kouno T, Nakada K, Hino O, Watanabe S, Ando J, Iwadate M, Yamamoto M, Lee MS, Tanaka K, Komatsu M
  • Journal Title: J Cell Biol Volume: 193(2) Pages: 275-84
  • DOI: doi:10.1083/jcb.201102031
  • Peer Reviewed
• [Journal Article] The innate immune system in host mice targets cells with allogenic mitochondrial DNA (2010)
  • Author(s): Ishikawa K, Toyama-Sorimachi N, Nakada K, Morimoto M, Imanishi H, Yoshizaki M, Sasawatari S, Niikura M, Takenaga K, Yonekawa H, Hayashi J
  • Journal Title: J Exp Med Volume: 207(11) Pages: 2297-305
  • DOI: doi10.1084/jem.20092296
  • 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, Yonekawa H
  • Journal Title: Biochem Biophys Res Commun Volume: 401(1) Pages: 26-31
  • DOI: doi:10.1016/j.bbrc.2010.08.143
  • Peer Reviewed
• [Journal Article] p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria (2010)
  • Author(s): Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou YS, Kimura M, Sato S, Hattori N, Komatsu M, Tanaka K, Matsuda N
  • Journal Title: Genes Cells Volume: 15(8) Pages: 887-900
  • DOI: doi:10.1111/j.1365-2443.2010.01426.x
  • 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 Lett Volume: 584(18) Pages: 3943-8
  • DOI: doi:10.1016/j.febslet.2010.07.048
  • Peer Reviewed
• [Journal Article] Mitochondrial respiration defects modulate differentiation but not proliferation of hematopoietic stem and progenitor cells (2010)
  • Author(s): Inoue S, Noda S, Kashima K, Nakada K, Hayashi J, Miyoshi H
  • Journal Title: FEBS Lett Volume: 584(15) Pages: 3402-9
  • DOI: doi:10.1016/j.febslet.2010.06.036
  • Peer Reviewed
• [Journal Article] Lactic acidemia in the pathogenesis of mice carrying mitochondrial DNA with a deletion (2010)
  • Author(s): Ogasawara E, Nakada K, Hayashi J
  • Journal Title: Hum Mol Genet Volume: 19(16) Pages: 3179-89
  • DOI: doi:10.1093/hmg/ddq228
  • Peer Reviewed
• [Presentation] ミトコンドリア糖尿病のマウス逆遺伝学 (2012)
  • Author(s): 中田和人、林純一
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] 病原性ミトコンドリアゲノム変異のマウス逆遺伝学 (2012)
  • Author(s): 中田和人、林純
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-02
• [Presentation] Reverse geneticstudies on mammalian mtDNA mutations (2011)
  • Author(s): Nakada K, Hayashi J
  • Organizer: European Meeting on Mitochondrial Pathology (Euromit 8)
  • Place of Presentation: Spain
  • Year and Date: 2011-06-21
• [Presentation] Reverse genetic studies on defects of mitochondrial central dogma (2011)
  • Author(s): Nakada K
  • Organizer: UCL-JSPS International Symposium
  • Place of Presentation: UK
  • Year and Date: 2011-02-10
• [Presentation] ミトコンドリアセントラルドグマの破綻病理 (2010)
  • Author(s): 中田和人、小笠原絵美、北潔、林純一
  • Organizer: BMB2010, ワークショップ「ミトコンドリア研究の最前線:基礎生命科学から臨床まで」
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Mouse models of mtDNA defects (2010)
  • Author(s): Nakada K, Hayashi J
  • Organizer: Mitochondrial Medicine 2010
  • Place of Presentation: Tokyo
  • Year and Date: 2010-06-18
• [Presentation] モデルマウスから得られた新知見 (2010)
  • Author(s): 中田和人
  • Organizer: 第113回日本小児学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-04-23
• [Presentation] ミトコンドリア遺伝子疾患における乳酸産生とその病原性 (2009)
  • Author(s): 中田和人、小笠原絵美、林純一
  • Organizer: 第32回日本分子生物学会大会ワークショップ「代謝適応と破綻に見る新たなミトコンドリア機能研究」
  • Place of Presentation: 神戸
  • Year and Date: 2009-12-12
• [Book] 細胞生物学 (2012)
  • Author(s): 沼田治、千葉智樹、中野賢太郎、中田和人
  • Total Pages: 203
  • Publisher: 化学同人
• [Remarks] ホームページ
  • URL: http://www.biol.tsukuba.ac.jp/~jih-kzt/