You Yanjing, Wang Huijuan, Wang Qing, Yu Zongyang, Zhao Zhongquan, Zhuang Liying, Zeng Shengyuan, Zheng Jinyang, 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, Fuzhou 350025, Fujian, P.R. China.
Graduate College of Fujian Medical University, Fuzhou 350025, China.
Open Med (Wars). 2023 Oct 6;18(1):20230798. doi: 10.1515/med-2023-0798. eCollection 2023.
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.
慢性阻塞性肺疾病（COPD）通常由吸烟引起。含FUN14结构域蛋白1（FUNDC1）在香烟烟雾提取物（CSE）处理的BEAS-2B细胞的线粒体自噬和凋亡中起重要作用。本研究探讨了FUNDC1在CSE处理的BEAS-2B细胞线粒体功能障碍和凋亡中的作用机制。采用免疫共沉淀法分析泛素特异性肽酶19（USP19）与FUNDC1之间的相互作用。测定了USP19基因敲低和/或FUNDC1过表达对15% CSE处理的BEAS-2B细胞的存活、凋亡、线粒体膜电位和氧消耗率（OCR）的影响。在BEAS-2B细胞中，CSE抑制细胞存活，促进凋亡，增加USP19和FUNDC1的表达，增加LC3 II与LC3 I的比值（LC3 II/I），并降低线粒体膜电位和TOM20水平。在CSE处理的BEAS-2B细胞中，USP19基因敲低降低了FUNDC1和LC3 II/I，增加了TOM20水平，改善了细胞存活、线粒体膜电位和OCR，并抑制了凋亡。USP19使FUNDC1去泛素化。FUNDC1过表达抑制了USP19基因敲低对CSE处理的BEAS-2B细胞的影响。总体而言，降低USP19表达通过下调FUNDC1减轻CSE诱导的BEAS-2B细胞线粒体功能障碍，为COPD中FUNDC1调控的分子机制提供了新的见解。
