Title:Role of Mitophagy in Cigarette Smoke-induced Lung Epithelial
Cell Injury In Vitro
Volume: 23
Issue: 10
Author(s): Suwen Wang, Xiaomin Song, Liangyu Wei, Qi Liu, Chenfei Li and Jiong Wang*
Affiliation:
- Department of Respiratory and Critical Care Medicine, The Geriatric Institute of Anhui, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China
Keywords:
Cigarette smoke, lung epithelial cell, mitochondria, mitophagy, necroptosis, COPD.
Abstract:
Background: Mitochondria mediate airway inflammatory responses to cigarette
smoke (CS). Removal of damaged or defective mitochondrial (mitophagy) may
prevent the detrimental impact of CS extract (CSE) on airway and lung epithelial cells.
Methods: We studied the effect of a mitophagy activator (Urolithin A, UA) and a mitophagy
inhibitor (Liensinine diperchlorate, Ld) on CSE-exposed alveolar (A549) and
airway (BEAS-2B) epithelial cell proliferation, intracellular and mitochondrial ROS,
inflammatory response, mitochondrial membrane potential (Δψm), mitochondrial
morphology, mitochondrial complex activities, and protein levels of mitochondrial fission
(DRP1, MFF) and mitophagy (SQSTM1/p62, LC3B). In both cell types, CSE exposure
led to increased intracellular and mitochondrial oxidative stress, decreased
Δψm and resulted in structural disruption of the mitochondrial network. CSE increased
the expression of DRP1, MFF and SQSTM1/p62 while decreasing LC3B-II/I protein
expression ratio. CSE also increased inflammatory (IL-1β, IL-6, IL-18, CXCL1, CXCL8)
and necroptosis factors (RIPK1, RIPK3, MLKL) mRNA expression.
Results: Pre-treatment with UA attenuated CSE-induced oxidative stress, inflammatory
and necroptosis gene expression and restored mitochondrial structure and function.
UA also prevented CSE-evoked increases in DRP1, MFF and SQSTM1/p62 protein
expression and increased LC3B-II/I ratio. Conversely, pre-treatment with Ld aggravated
CSE-induced cellular and mitochondrial responses.
Conclusion: In conclusion, mitophagy mediates CSE-induced damage and inflammation
of lung epithelial cells and may represent a therapeutic target in CS-driven diseases.