FUNDC1 mediated mitochondria-dependent ferroptosis of epithelial cells in model of asthma by FBXL2/ar/GPX4 signaling pathway of SUMO1 at K136.

Abstract\nPLAIN LANGUAGE SUMMARYThis study aimed to explore the critical role of FUNDC1 on epithelial cells in model of asthma. Patients with asthma and normal healthy volunteers were obtained from our hospital. The serum of FUNDC1 mRNA expression was down-regulated in patients with asthma. Meanwhile, the serum of FUNDC1 mRNA expression was positive correlation with IgE and anti-HDM IgE protein. FUNDC1 expression in lung tissue of mice model was decreased in mice model of asthma. Sh-FUNDC1 enhanced asthma in mice model of asthma. FUNDC1 up-regulation reduced IL-4, IL-5, IL-10 and IL-13 activity levels <italic>in vitro</italic> model of asthma.FUNDC1 down-regulation promoted IL-4, IL-5, IL-10 and IL-13 activity levels <italic>in vitro</italic> model of asthma. FUNDC1 reduced ferroptosis of epithelial cells in model of asthma through the inhibition of mitochondrial damage. FUNDC1 induced FBXL2 and AR protein expression in model of asthma. FUNDC1 interlinked with FBXL2 is modified by SUMO1 at K136. FBXL2, ASN-205, GLN-204, ARG-235, and GLN-237 form hydrogen bonds with FUNDC1's ASP-15, ASP-16, GLU-25, and ARG-29, with lengths of 2.3, 3.1, 2.9, 2.3, and 2.9 Å, respectively. The induction of FBXL2 reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma. The inhibition of AR reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma Overall, FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease.FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease. [ABSTRACT FROM AUTHOR]