Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models

Disease Models & Mechanisms

Antoon Opperhuizen¹  Frederik-Jan van Schooten¹  Alexander H. V. Remels¹  Christy B. M. Tulen¹  Phyllis J. J. Jessen¹  Pieter S. Hiemstra²  Daan Beentjes²  Ying Wang²  Dennis K. Ninaber²  Niki L. Reynaert³ 

[1] Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD Maastricht, The Netherlands;Department of Pulmonology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands;Department of Respiratory Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, PO Box 616, 6200 MD Maastricht, The Netherlands;

关键词: autophagy;    cell model;    cigarette smoke;    culture methods;    human primary bronchial epithelial cells;    mitochondrial metabolism;   

DOI  :  10.1242/dmm.049247

来源: DOAJ

【 摘 要 】

Exposure to cigarette smoke (CS) is the primary risk factor for developing chronic obstructive pulmonary disease. The impact of CS exposure on the molecular mechanisms involved in mitochondrial quality control in airway epithelial cells is incompletely understood. Undifferentiated or differentiated primary bronchial epithelial cells were acutely/chronically exposed to whole CS (WCS) or CS extract (CSE) in submerged or air–liquid interface conditions. Abundance of key regulators controlling mitochondrial biogenesis, mitophagy and mitochondrial dynamics was assessed. Acute exposure to WCS or CSE increased the abundance of components of autophagy and receptor-mediated mitophagy in all models. Although mitochondrial content and dynamics appeared to be unaltered in response to CS, changes in both the molecular control of mitochondrial biogenesis and a shift toward an increased glycolytic metabolism were observed in particular in differentiated cultures. These alterations persisted, at least in part, after chronic exposure to WCS during differentiation and upon subsequent discontinuation of WCS exposure. In conclusion, smoke exposure alters the regulation of mitochondrial metabolism in airway epithelial cells, but observed alterations may differ between various culture models used. This article has an associated First Person interview with the joint first authors of the paper.

【 授权许可】

Unknown