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An approach from crosstalks of nuclei-mitochondria to disease mechanisms of mitochondrial diseases

Research Project

Project/Area Number 16K18535
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionUniversity of Tsukuba

Principal Investigator

Ishikawa Kaori  筑波大学, 生命環境系, 助教 (40734827)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsミトコンドリアDNA / ミトコンドリア・ダイナミクス / Drp1 / ミトコンドリア分裂 / ミトコンドリア病 / 病態発症機構 / ミトコンドリア / mtDNA / 呼吸機能 / 貧血 / 血球分化 / モデルマウス / ΔmtDNA / Mitophagy
Outline of Final Research Achievements

Disease phenotypes of the model mice with a pathogenic mitochondrial DNA (mtDNA) mutation and dysfunction of Drp1, a mitochondrial fission factor, were analyzed. Drp1 dysfunction made disease phenotypes induced by the mtDNA mutation more severer. These results indicate that Drp1-mediated mitohondrial fission suppresses disease phenotypes induced by the mtDNA mutation, and also suggest that there are important crosstalks between mitochondria and nuclei.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリア病はその病態発症機構がほとんど理解されておらず、治療法はおろか正確な診断すらもままならない困難な疾患である。本研究は、ミトコンドリアDNA(mtDNA)に突然変異を有することで病態を発症するマウスに、核DNAにコードされたミトコンドリア関連遺伝子の機能不全を共存させることによって、核DNAのミトコンドリア関連遺伝子とミトコンドリア機能との間にクロストークがあることを見出した。この成果は、ミトコンドリア病の複雑な病態発症機構の一端を明らかにすることにつながると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Remarks (4 results)

  • [Journal Article] Concentration of mitochondrial DNA mutations by cytoplasmic transfer from platelets to cultured mouse cells.2019

    • Author(s)
      Ishikawa K, Kobayashi K, Yamada A, Umehara M, Oka T, Nakada K.
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 3 Pages: 0213283-0213283

    • DOI

      10.1371/journal.pone.0213283

    • NAID

      120007133505

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquired expression of mutant Mitofusin 2 causes progressive neurodegeneration and abnormal behavior2019

    • Author(s)
      Ishikawa K, Yamamoto S, Hattori S, Nishimura N, Tani H, Mito T, Matsumoto H, Miyakawa T, Nakada K
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 9 Pages: 1588-1604

    • DOI

      10.1523/jneurosci.2139-18.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mito-mice∆ and mitochondrial DNA mutator mice as models of human osteoporosis caused not by aging but by hyperparathyroidism2018

    • Author(s)
      Mito Takayuki、Tani Haruna、Suzuki Michiko、Ishikawa Kaori、Nakada Kazuto、Hayashi Jun-Ichi
    • Journal Title

      Experimental Animals

      Volume: 67 Issue: 4 Pages: 509-516

    • DOI

      10.1538/expanim.18-0060

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are embryonic lethal.2018

    • Author(s)
      Tani H, Ohnishi S, Shitara H, Mito T, Yamaguchi M, Yonekawa H, Hashizume O, Ishikawa K, Nakada K, Hayashi JI.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 425-425

    • DOI

      10.1038/s41598-017-18828-3

    • NAID

      120007134501

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of pharmacokinetic/efficacy analysis of an investigational kisspeptin analog, TAK-448, in quantitatively evaluating anti-tumor growth effect in the rat VCaP androgen-sensitive prostate cancer model.2018

    • Author(s)
      Ishikawa K, Tanaka A, Kogame A, Watanabe T, Tagawa Y, Matsui H.
    • Journal Title

      Eur J Pharmacol.

      Volume: 828 Pages: 126-134

    • DOI

      10.1016/j.ejphar.2018.03.032

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats2017

    • Author(s)
      Kanai N, Endo N, Ohkura S, Wakabayashi Y, Matsui H, Matsumoto H, Ishikawa K, Tanaka A, Watanabe T, Okamura H, Tanaka T.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 63 Issue: 3 Pages: 305-310

    • DOI

      10.1262/jrd.2016-184

    • NAID

      130007314605

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice2017

    • Author(s)
      Shimizu Akinori、Tani Haruna、Takibuchi Gaku、Ishikawa Kaori、Sakurazawa Ryota、Inoue Takafumi、Hashimoto Tetsuo、Nakada Kazuto、Takenaga Keizo、Hayashi Jun-Ichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 1 Pages: 252-257

    • DOI

      10.1016/j.bbrc.2017.09.035

    • NAID

      120007134703

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel mutation in TAZ causes mitochondrial respiratory chain disorder without cardiomyopathy2016

    • Author(s)
      Borna NN, Kishita Y, Ishikawa K, Nakada K, Hayashi JI, Tokuzawa Y, Kohda M, Nyuzuki H, Yamashita-Sugahara Y, Nasu T, Takeda A, Murayama K, Ohtake A, Okazaki Y
    • Journal Title

      J Hum Genet

      Volume: 62 Issue: 5 Pages: 539-547

    • DOI

      10.1038/jhg.2016.165

    • NAID

      40021210340

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mutations in mitochondrial DNA regulate mitochondrial diseases and metastasis but do not regulate aging.2016

    • Author(s)
      Hayashi JI, Hashizume O, Ishikawa K, Shimizu A.
    • Journal Title

      Curr Opin Genet Dev.

      Volume: 未定 Pages: 63-67

    • DOI

      10.1016/j.gde.2016.03.004

    • NAID

      120007135211

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] マウス培養細胞は組織よりも高い割合のミトコンドリアDNA突然変異を許容できる2018

    • Author(s)
      石川香、小林晃平、山田亮仁、梅原萌、岡敏彦、中田和人
    • Organizer
      第18回日本ミトコンドリア学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The D210V mutation of Mfn2 in neurons induces different pathologies in severity depends on its expression timing2018

    • Author(s)
      Kaori Ishikawa
    • Organizer
      Keystone Symposia “Mitochondrial Biology”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The importance of Mfn2 in neuronal function from juvenile to adult phase2018

    • Author(s)
      Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Takayuki Mito, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada
    • Organizer
      International YoungMito “The 1st International Mitochondria Meeting for Young Scientists”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Progressive neurodegeneration and abnormal behavior were caused by acquired expression of mutant Mitofusin 2 in neurons2018

    • Author(s)
      Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Takayuki Mito, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada
    • Organizer
      The 41st Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The importance of Mfn2 in neuronal function from juvenile to adult phase2018

    • Author(s)
      Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Takayuki Mito, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada
    • Organizer
      The 1st International Mitochondria Meeting for Young Scientists
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The D210V mutation of Mfn2 in neurons induces different pathologies in severity depends on its expression timing2018

    • Author(s)
      Kaori Ishikawa, Satoshi Yamamoto, Satoko Hattori, Naoya Nishimura, Takayuki Mito, Hirokazu Matsumoto, Tsuyoshi Miyakawa, Kazuto Nakada
    • Organizer
      Keystone Symposia -Mitochondrial Biology (Z1)-
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経におけるMfn2のD210V突然変異は発現時期によって重症度の異なる病態を引き起こす2017

    • Author(s)
      石川香、山本智、服部聡子、西村尚也、三藤崇行、松本寛和、宮川剛、中田和人
    • Organizer
      第17回日本ミトコンドリア学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミトコンドリア病の多様な病態発症機構の理解に向けたアプローチ~核-ミトコンドリア間クロストーク~.2016

    • Author(s)
      石川香、堅田俊、小笠原絵美、本間耀、石原孝也、三藤崇行、三原勝芳、林純一、石原直忠、中田和人.
    • Organizer
      第39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
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] The importance of mitochondrial fission in preventing disease phenotypes induced by a pathogenic mtDNA mutation.2016

    • Author(s)
      Ishikawa K, Katada S, Ogasawara E, Homma Y, Ishihara T, Mito T, Mihara K, Hayashi JI, Ishihara N, Nakada K.
    • Organizer
      The 13th Conference of Asian Society for Mitochondrial Research and Medicine [ASMRM] and The 16th Conference of Japanese Siciety of Mitochondrial Research and Medicine [J-mit].
    • Place of Presentation
      TKPガーデンシティ品川, Shinagawa, Tokyo, Japan.
    • Year and Date
      2016-10-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 筑波大学生命環境系 中田・石川研HP

    • URL

      http://www.biol.tsukuba.ac.jp/nakada_ishikawa/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 筑波大学 注目の研究

    • URL

      http://www.tsukuba.ac.jp/attention-research/r201903291000.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 筑波大学 生命環境系 中田・石川研究室

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/

    • Related Report
      2017 Research-status Report
  • [Remarks] 筑波大学 生命環境系 中田・石川研究室

    • URL

      http://www.biol.tsukuba.ac.jp/~jih-kzt/index.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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