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Role of mitophagy and mitochondrial dynamics in cigarette smoke-induced bronchial epithelial cell senescence.

Research Project

Project/Area Number 25860661
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

HARA Hiromichi  東京慈恵会医科大学, 医学部, 講師 (70398791)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsCOPD / ミトコンドリア動態 / マイトファジー / ミトコンドリア
Outline of Final Research Achievements

We demonstrated the role of mitochondrial dynamics in human bronchial epithelial cell (HBEC) senescence induced by cigarette smoke extract (CSE) exposure. CSE induced mitochondrial fragmentation and mitochondrial ROS production, which were responsible for acceleration of cellular senescence. Mitochondrial fragmentation itself increased mitochondrial ROS production and cellular senescence. Treatment of antioxidant inhibited both CSE-induced and mitochondria fragmentation-induced cellular senescence. Accumulation of fragmented mitochondria with increased ROS by decreased mitophagy accelerated cellular senescence. Mitochondria in bronchial epithelial cells were prone to be more fragmented in COPD lung tissues in electron microscopic evaluation. Taken together, mitochondrial fragmentation and decreased mitophagy in lung may be involved in COPD pathogenesis through the acceleration of cellular senescence.

Report

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

    (3 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.2015

    • Author(s)
      Ito S, Araya J, Kurita Y, Kobayashi K, Takasaka N, Yoshida M, Hara H, Minagawa S, Wakui H, Fujii S, Kojima J, Shimizu K, Numata T, Kawaishi M, Odaka M, Morikawa T, Harada T, Nishimura SL, Kaneko Y, Nakayama K, Kuwano K.
    • Journal Title

      Autophagy

      Volume: 未定

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence.2014

    • Author(s)
      Takasaka N, Nakayama K, et al.
    • Journal Title

      J Immunol

      Volume: 192 Issue: 3 Pages: 958-968

    • DOI

      10.4049/jimmunol.1302341

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence.2013

    • Author(s)
      Hara H, Araya J, Ito S, Kobayashi K, Takasaka N, Yoshii Y, Wakui H, Kojima J, Shimizu K, Numata T, Kawaishi M, Kamiya N, Odaka M, Morikawa T, Kaneko Y, Nakayama K, Kuwano K.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 305(10) Issue: 10 Pages: L737-L746

    • DOI

      10.1152/ajplung.00146.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed

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Published: 2014-07-25   Modified: 2019-07-29  

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