Hypervulnerability to sound-exposure through impaired adaptive proliferation of peroxisomes

A deficiency of pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of deafness. Pejvakin-deficient (Pjvk-/-) mice also exhibited variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggested a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation showed that the cochlear sensory hair cells and auditory pathway neurons of Pjvk-/- mice and patients were exceptionally vulnerable to sound. Pjvk-/- cochleas displayed features of marked oxidative stress and impaired anti-oxidant defenses. We showed that pejvakin is associated with peroxisomes, and is required for the oxidative stress-induced proliferation of these organelles. In Pjvk-/- hair cells, peroxisomes displayed structural abnormalities after the onset of hearing. Noise-exposure of wild-type mice rapidly upregulated Pjvk cochlear transcription, and triggered peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the anti-oxidant activity of peroxisomes protects the auditory system against noise-induced damage.

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Delmaghani S, Defourny J, Aghaie A, Beurg M, Dulon D, Thelen N, Perfettini I, Zelles T, Aller M, Meyer A, Emptoz A, Giraudet F, Leibovici M, Dartevelle S, Soubigou G, Thiry M, Vizi ES, Safieddine S, Hardelin JP, Avan P, Petit C