The influence of mitochondrial biological function on sudden sensorineural hearing loss: Exploring potential mechanisms and associations through Mendelian randomization analysis

Mitochondrial dysfunction, particularly involving energy metabolism, oxidative stress, and structural integrity, is recognized as a critical factor in the pathogenesis of hearing loss. However, evidence regarding a potential association between mitochondrial function and sudden sensorineural hearing loss (SSNHL) remains limited. This study aims to explore the potential causal relationship between mitochondrial biological function and SSNHL using Mendelian randomization (MR) analysis. We utilized genome-wide association study data on SSNHL from the FinnGen database, along with mitochondria-related genome-wide association study summary statistics from previously published studies. Inverse variance weighting served as the primary MR method, using genetic instruments associated with mitochondrial biological function to estimate their effects on SSNHL risk. Sensitivity analyses-including MR-Egger regression, MR-PRESSO, and leave-one-out analysis-were conducted to assess the robustness of the findings and to exclude potential biases. Three mitochondrial proteins were found to exhibit potential causal effects on SSNHL. MUL1 was identified as a potential risk factor, whereas HINT2 and GRPEL1 appeared to serve as potential protective factors. This study provides evidence supporting a potential causal role of mitochondrial biological function in SSNHL. The findings offer novel insights into the mechanistic underpinnings of SSNHL and emphasize the importance of mitochondrial pathways in its pathophysiology. These results may encourage otolaryngologists to consider targeting mitochondrial energy metabolism in the development of more effective clinical prevention and treatment strategies for SSNHL.