Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway

Abstract

Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory hair cells within the cochlea, yet the pursuit of efficacious therapeutic interventions remains an ongoing challenge. Previous investigations have illuminated the role of mitochondrial dysfunction in precipitating cellular apoptosis, and mitophagy has emerged as a promising mechanism to ameliorate such dysfunction. Additionally, it has been noted that metformin possesses the specific ability to induce mitophagy. Herein, our objective is to explore the protective effects of metformin-induced mitophagy against apoptosis in auditory hair cells (HEI-OC1 cells) and explore its potential mechanisms. Our results revealed that metformin effectively triggered mitophagy in HEI-OC1 cells. Moreover, metformin treatment showed the ability to prevent tert-butyl hydroperoxide (TBHP) induced mitochondrial dysfunction and intrinsic apoptotic pathways. Mechanistically, we discovered that metformin activates AMP-activated protein kinase (AMPK) signaling in HEI-OC1 cells stimulated by TBHP, thereby triggering mitophagy. Overall, our results suggest that metformin may represent a promising and innovative therapeutic strategy for mitigating the onset of hearing loss.