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

• Project/Area Number: 25860661
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Jikei 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: ¥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)
• Keywords: COPD / 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.

Research Products

• [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
  • 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
  • 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
  • Peer Reviewed