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Published on: January 10, 2015
Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting
Yanjing You1, Huijuan Wang2, Qing Wang3
1Department of Respiratory and Critical Care Medicine, Fuzhou General Hospital of Fujian Medical University, Dongfang Hospital of Xiamen University, 900TH Hospital of Joint Logistics Support Force, PLA, Fuzhou 350025, Fujian, P.R. China.
Abstract:
Chronic obstructive pulmonary disease (COPD) is commonly caused by smoking. FUN14 domain-containing protein 1 (FUNDC1) plays a fundamental role in mitochondrial autophagy and apoptosis in cigarette smoke extract (CSE)-treated BEAS-2B cells. The present study investigated the mechanism of action of FUNDC1 in mitochondrial dysfunction and apoptosis in CSE-treated BEAS-2B cells. The interaction between ubiquitin-specific peptidase 19 (USP19) and FUNDC1 was analyzed using co-immunoprecipitation. Effects of USP19 knockdown and/or FUNDC1 overexpression on the survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR) of BEAS-2B cells treated with 15% CSE were determined. In BEAS-2B cells, CSE inhibited cell survival, promoted apoptosis, increased the expression of USP19 and FUNDC1, increased the ratio of LC3 II to LC3 I (LC3 II/I), and decreased mitochondrial membrane potential and TOM20 levels. In CSE-treated BEAS-2B cells, USP19 knockdown reduced FUNDC1 and LC3 II/I, increased the levels of TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis. USP19 deubiquitinates FUNDC1. FUNDC1 overexpression inhibited the effect of USP19 knockdown in CSE-treated BEAS-2B cells. Overall, decreasing USP19 expression alleviates CSE-induced mitochondrial dysfunction in BEAS-2B cells by downregulating FUNDC1, providing novel insights into the molecular mechanism of FUNDC1 regulation in COPD.
Insights
Reducing ubiquitin-specific peptidase 19 (USP19) alleviates cigarette smoke extract (CSE)-induced mitochondrial dysfunction in chronic obstructive pulmonary disease (COPD) cells. This occurs by downregulating FUN14 domain-containing protein 1 (FUNDC1), offering new therapeutic insights.
Area of Science:
- Cell Biology
- Molecular Biology
- Pulmonology
Background:
- Chronic obstructive pulmonary disease (COPD) is primarily linked to smoking.
- FUN14 domain-containing protein 1 (FUNDC1) is implicated in mitochondrial autophagy and apoptosis.
- Cigarette smoke extract (CSE) induces mitochondrial dysfunction and apoptosis in lung cells.
Purpose of the Study:
- To investigate the role of FUNDC1 in CSE-induced mitochondrial dysfunction and apoptosis.
- To elucidate the mechanism by which ubiquitin-specific peptidase 19 (USP19) affects FUNDC1 in CSE-treated cells.
Main Methods:
- Co-immunoprecipitation to analyze USP19-FUNDC1 interaction.
- USP19 knockdown and FUNDC1 overexpression in CSE-treated BEAS-2B cells.
- Assessment of cell survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR).
Main Results:
- CSE increased USP19 and FUNDC1 expression, LC3 II/I ratio, and apoptosis, while decreasing cell survival, mitochondrial membrane potential, and TOM20 levels.
- USP19 knockdown reduced FUNDC1 and LC3 II/I, increased TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis.
- USP19 deubiquitinates FUNDC1, and FUNDC1 overexpression counteracted the protective effects of USP19 knockdown.
Conclusions:
- USP19 deubiquitinates FUNDC1, promoting CSE-induced mitochondrial dysfunction and apoptosis.
- Decreasing USP19 expression alleviates CSE-induced mitochondrial damage by downregulating FUNDC1.
- This study reveals a novel molecular mechanism of FUNDC1 regulation in COPD pathogenesis.
