MA12.04 Mitochondrial-Related Proteins, PGAM5 and FUNDC1, in COPD-Associated Non-Small Cell Lung Carcinoma

Kwong, Francois Ng Kee; Nicholson, Andrew G.; Adcock, Ian M.; Chung, Fan

doi:10.1016/j.jtho.2016.11.472

Cited by 1 publication

(4 citation statements)

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“…Another study has also indicated that accumulation of FUNDC1 is presented at the MAM in the hypoxia environment . Furthermore, FUNDC1 was also verified to upregulate in COPD patients, which was consistent with the findings in this study. Moreover, the data in this present study implied that the biomarkers related to small airway function, including FEV0.3, FEF25‐75, and PEF, and the levels of IL‐6 and TNF‐α were elevated in COPD mice provoked by CS.…”

Section: Discussionsupporting

confidence: 91%

“…25 Another study has also indicated that accumulation of FUNDC1 is presented at the MAM in the hypoxia environment. 26 Furthermore, FUNDC1 was also verified to upregulate in COPD patients, 14 which was consistent with the findings in this study. Moreover, the data in this F I G U R E 4 FUNDC1 silencing inhibits CSE-induced mitochondrial autophagy and necrosis of hBECs by regulating DRP1.…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, FUNDC1 has important roles to play in exerting crucial effects on autophagy and apoptosis of hypoxic cells . A prior study has provided evidence demonstrating that FUNDC1 is overexpressed in COPD . As discussed above, it has been hypothesized that FUNDC1 is involved in COPD via regulation of mitochondrial autophagy.…”

Section: Introductionmentioning

confidence: 96%

“…13 A prior study has provided evidence demonstrating that FUNDC1 is overexpressed in COPD. 14 As discussed above, it has been hypothesized that FUNDC1 is involved in COPD via regulation of mitochondrial autophagy. Therefore, by analyzing the expression of FUNDC1 in COPD, the effects on mitochondrial autophagy and apoptosis, and their underlying mechanism in the pathogenesis of COPD were able to be understood.…”

Section: Introductionmentioning

confidence: 99%

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Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment

Wen

Liu

et al. 2019

J of Cellular Biochemistry

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Chronic obstructive pulmonary disease (COPD) is a major global epidemic with increasing incidence worldwide. The pathogenesis of COPD is involved with mitochondrial autophagy. Recently, it has been reported that FUN14 domain containing 1 (FUNDC1) is a mediator of mitochondrial autophagy. Therefore, we hypothesized that FUNDC1 was involved in cigarette smoke (CS)‐induced COPD progression by regulating mitochondrial autophagy. In vitro cigarette smoke extract (CSE)‐treated human bronchial epithelial cell (hBEC) Beas‐2B cell line and in vivo CS‐induced COPD mouse models were developed, in which FUNDC1 expression was measured. Next, whether FUNDC1 interacted with dynamin‐related protein 1 (DRP1) in COPD was investigated. The functional mechanism of FUNDC1 in COPD was evaluated through gain‐ or loss‐of‐function studies. Then, pulmonary function, mitochondrial transmembrane potential (MTP) and mucociliary clearance (MCC) were examined. Levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) and expression of autophagy‐specific markers (light chain 3 [LC3] II, LC3 I, and Tom20) were measured. Finally, apoptosis and mitochondrial autophagy were assessed. FUNDC1 was highly expressed in CSE‐treated hBECs and COPD mice. Meanwhile, FUNDC1 was proved to interact with DRP1 in CSE‐treated cells. Moreover, in CSE‐treated hBECs, silencing FUNDC1 was observed to reduce levels of IL‐6 and TNF‐α, and MTP but increase MCC, and inhibit CSE‐induced mitochondrial autophagy and Beas‐2B cell apoptosis, which was consistent with the trend in COPD mouse models. In addition, pulmonary function of COPD mouse models was increased in response to FUNDC1 silencing. Finally, silencing of DRP1 also inhibited mitochondrial autophagy and Beas‐2B cell apoptosis. Collectively, FUNDC1 silencing could suppress the progression of COPD by inhibiting mitochondrial autophagy and hBEC apoptosis through interaction with DRP1, highlighting a potential therapeutic target for COPD treatment.

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Section: Discussionsupporting

confidence: 91%