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

2014 Fiscal Year Final Research Report

• 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
• Keywords: COPD / ミトコンドリア動態 / マイトファジー

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.

Free Research Field

呼吸器内科