Pejvakin-mediated pexophagy protects auditory hair cells against noise-induced damage

Significance Noise-induced hearing loss is a highly prevalent form of sensorineural hearing impairment affecting individuals of all ages. Noise exposure triggers a rapid increase in reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting in hearing loss. Here we describe a novel mechanism of protection against noise-induced auditory hair cell damage. In response to sound exposure, pejvakin, a peroxisome-associated protein, acts as an ROS sensor and recruits the autophagy machinery to trigger the degradation of peroxisomes (pexophagy) damaged by oxidative stress. We characterized the pejvakin interactions involved in this process. We provide evidence that pejvakin-mediated pexophagy plays a key role in controlling peroxisome proliferation and protecting auditory hair cells against noise-induced damage.