Coenzyme Q9 Derived from Oudemansiella raphanipes Attenuates Mucin Biosynthesis Induced by Pseudomonas aeruginosa Pyocyanin in Human Bronchial Epithelial Cells

Pyocyanin is a potent redox-cycling secondary metabolite secreted by the respiratory pathogen Pseudomonas aeruginosa. During chronic P. aeruginosa infections, pyocyanin induces persistent oxidative stress in airway epithelial cells, ultimately leading to goblet cell hyperplasia and metaplasia alongside mucus hypersecretion. Because PCN triggers a redox imbalance by rapid depletion of host antioxidants, restoring cellular antioxidative capacity is essential to mitigate its pathophysiology. Herein, we demonstrate that Coenzyme Q9 (CoQ9) from the edible mushroom Oudemansiella raphanipes attenuates pyocyanin-induced mucus hypersecretion in primary human bronchial epithelial cells by restoring mitochondrial integrity to alleviate oxidative stress. CoQ9 pretreatment attenuates MUC5AC and MUC5B mucin expression by inactivating mucin-promoting signaling cascades, including the EGFR-AKT/ERK1/2 and STAT6-SPDEF axes. In addition to its reactive oxygen species scavenging properties, CoQ9 significantly downregulated pyocyanin-induced mitochondrial superoxide generation by restoring the SIRT3-SOD2 axis. Specifically, CoQ9 pretreatment improved mitochondrial integrity by preserving PINK1-mediated mitophagy and enhancing mitochondrial biogenesis through activation of the AMPK-PGC1α axis, thereby restoring ATP levels under PCN exposure.