The Role of Mitochondrial Homeostasis in the Pathogenesis of Chronic Rhinosinusitis
Babak Ghalehbaghi, Morteza Fallahpour, Mohammad Nabavi, Maryam Jalessi, Hadi Ghanbari, Nasibeh Khayer, Farzad Taghizadeh‐HesaryABSTRACT
Background
Chronic rhinosinusitis (CRS) is a common clinical condition characterized by persistent inflammation of the nasal and sinus mucosa. While inflammatory endotypes are well‐described, the upstream metabolic dysregulations that initiate and perpetuate inflammation remain poorly defined. This review examines how mitochondrial metabolism, biogenesis, and dysfunction contribute to CRS pathogenesis.
Methods
A comprehensive literature search was performed up to November 2025 using PubMed/MEDLINE, Web of Science, and ScienceDirect. Search terms included “chronic rhinosinusitis,” “mitochondria,” “oxidative stress,” “reactive oxygen species,” “inflammation,” and “epithelial barrier,” together with related keywords and synonyms. Experimental, mechanistic, and translational studies exploring mitochondrial involvement in CRS were included.
Results
Evidence from multiple experimental studies demonstrates that mitochondrial dysfunction is closely intertwined with key pathological processes in CRS. Mitochondria are damaged by diverse CRS‐related pathogenic factors leading to excessive reactive oxygen species production, impaired biogenesis, and disrupted membrane potential. These mitochondrial abnormalities amplify epithelial inflammation, oxidative stress, and barrier dysfunction, creating a self‐propagating vicious cycle in which mitochondrial injury and inflammation reinforce each other. Mitochondrial dysfunction also contributes to characteristic histopathological changes, including epithelial damage, ciliary impairment, and fibrin deposition.
Conclusions
Mitochondria play a pivotal role in CRS pathogenesis. Targeting this self‐amplifying cycle of Inflammation–oxidative stress–mitochondrial dysfunction therefore represents a promising therapeutic strategy for breaking the chronicity of CRS.