Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
You Yanjing,
Wang Huijuan,
Wang Qing,
Yu Zongyang,
Zhao Zhongquan,
Zhuang Liying,
Zeng Shengyuan,
Zheng Jinyang,
Wen Wen
Affiliations
You Yanjing
Department 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
Wang Huijuan
Graduate College of Fujian Medical University, Fuzhou350025, China
Wang Qing
Department of Respiratory and Critical Care Medicine, The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou350108, Fujian, China
Yu Zongyang
Department 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
Zhao Zhongquan
Department 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
Zhuang Liying
Graduate College of Fujian Medical University, Fuzhou350025, China
Zeng Shengyuan
Graduate College of Fujian Medical University, Fuzhou350025, China
Zheng Jinyang
Graduate College of Fujian Medical University, Fuzhou350025, China
Wen Wen
Department 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, No. 156, Xi’erhuan North Road, Gulou District, Fuzhou 350025, Fujian, P.R. China
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.
