UBC/UBA52 silencing restores PINK1-Parkin-mediated mitochondrial autophagy in allergic rhinitis

Abstract

Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract, and recent studies suggest that mitochondrial dysfunction may play a role in its pathogenesis. This study aimed to identify key genes related to AR and mitochondrial autophagy through bioinformatics analysis and to verify their functional roles in vitro. Transcriptomic data from the GEO database were analyzed, and ubiquitin C (UBC) and ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) were identified as potential genes associated with AR and mitophagy. In vitro , IL-13–stimulated human nasal epithelial cells (HNEpCs) were used to establish an AR model. RT-qPCR and Western blotting showed that UBC and UBA52 were significantly upregulated, while mitophagy-related genes PINK1 and Parkin were downregulated. Flow cytometry and TMRE staining demonstrated increased ROS levels and reduced mitochondrial membrane potential (MMP), indicating mitochondrial dysfunction. Co-immunoprecipitation confirmed an interaction between UBC and UBA52. Silencing UBC downregulated UBA52 expression, restored PINK1 and Parkin levels, decreased ROS accumulation, and improved MMP, suggesting potential reactivation of the PINK1–Parkin–mediated mitophagy pathway. These findings suggest that UBC and UBA52 may be involved in the regulation of mitophagy and contribute to mitochondrial dysfunction in AR. Targeting the UBC–UBA52 axis may provide a novel therapeutic strategy for restoring mitochondrial homeostasis in allergic inflammation.