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Segregation mechanism of human mitochondrial genome through TFAM

Research Project

Project/Area Number 24790324
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionJichi Medical University

Principal Investigator

KASASHIMA Katsumi  自治医科大学, 医学部, 講師 (80382844)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsミトコンドリアDNA / 分配 / TFAM / ミトコンドリア / ヌクレオイド
Outline of Final Research Achievements

The segregation of mitochondrial genome affects the transmission of mutant mitochondrial DNA (mtDNA) variant and clinical abnormalities of mitochondrial disorders. Recently, we clarified that human mitochondrial transcription factor A (TFAM) is required for equal distribution and symmetric segregation of mtDNA in cultured cells. To elucidate the molecular mechanism of the TFAM-mediated mtDNA segregation, we screened nucleoid factors involved in this process. We found a mitochondrial AAA+ chaperone Clp as a novel regulator. Because ClpX enhances the DNA-binding activity of TFAM in vitro, it is strongly suggested that ClpX regulates mtDNA segregation through quality control of TFAM.
By using separated fluorescent protein as reporter, we found that TFAM self-associates in mitochondria in vivo. The dimer mutant is actively degraded by proteasome system, suggesting that the self-interaction protects TFAM from degradation and regulates its expression levels.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (11 results)

All 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 5 results) Presentation (5 results)

  • [Journal Article] Dynamic regulation of mitochondrial genome maintenance in germ cells2014

    • Author(s)
      Kasashima K., et al.
    • Journal Title

      Reproductive Medicine and Biology

      Volume: 13 Issue: 1 Pages: 11-20

    • DOI

      10.1007/s12522-013-0162-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Translational repression of the McKusick-Kaufman syndrome transcript by unique upstream open reading frames encoding mitochondrial proteins with alternative polyadenylation sites2013

    • Author(s)
      Akimoto, C. Sakashita, E., Kasashima, K., Kuroiwa, K., Tominaga, K., Hamamoto, T., and Endo, H.
    • Journal Title

      Biochem Biophys Acta

      Volume: 1830 Issue: 3 Pages: 2728-2738

    • DOI

      10.1016/j.bbagen.2012.12.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type2013

    • Author(s)
      Tetsuka, S. Tominaga, K. Ohta, E. Kuroiwa, K. Sakashita, E. Kasashima, K. Hamamoto, T. Namekawa, M. Morita, M. Natsui, S. Morita, T. Tanaka, K. Takiyama, Y. Nakano, I. Endo, H.
    • Journal Title

      J Neurol Sci

      Volume: 335 Issue: 1-2 Pages: 48-57

    • DOI

      10.1016/j.jns.2013.08.022

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduction of malaria transmission by transgenic mosquitoes expressing an anti-sporozoite antibody in their salivary glands2013

    • Author(s)
      Sumitani M
    • Journal Title

      Insect Mol Biol

      Volume: in press Issue: 1 Pages: 1-11

    • DOI

      10.1111/j.1365-2583.2012.01168.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein.ClpX. Exp2012

    • Author(s)
      Kasashima, K., Sumitani, M., and Endo, H
    • Journal Title

      Cell Res

      Volume: 318 Issue: 18 Pages: 2335-2343

    • DOI

      10.1016/j.yexcr.2012.07.012

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリア膜の機能的新タンパク質類ープロヒビチン2012

    • Author(s)
      遠藤仁司、笠嶋克巳
    • Journal Title

      生体の科学

      Volume: 63 Pages: 432-433

    • Related Report
      2012 Research-status Report
  • [Presentation] ミトコンドリア内におけるTFAM間相互作用に必要なドメインの同定2014

    • Author(s)
      笠嶋克巳、遠藤仁司
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] TFAMによるミトコンドリアゲノム分配機構の解析2013

    • Author(s)
      笠嶋克巳
    • Organizer
      日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Molecular mechanism of TFAM-regulated mitochondrial DNA/Nucleoid distribution2013

    • Author(s)
      Katsumi Kasashima
    • Organizer
      The 4th International Symposium on Dynamics of Mitochondria
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトClpXはTFAMを介してミトコンドリアゲノムの分布を調節する2012

    • Author(s)
      笠嶋克巳
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] ミトコンドリアシャペロンClpXによるTFAM調節機構の解析2012

    • Author(s)
      笠嶋克巳
    • Organizer
      日本ミトコンドリア学会
    • Place of Presentation
      筑波大学
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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