Pejvakin-deficient mice and humans are hypervulnerable to sound exposure
•
Oxidative stress induces a pejvakin-dependent proliferation of peroxisomes
•
Peroxisome proliferation contributes to the physiological response to sound exposure
•
Pjvk gene transfer can rescue auditory dysfunction in Pjvk−/− mice
Summary
A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk−/−) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk−/− mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk−/− cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk−/− hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage.