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Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

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Delmaghani, Sedigheh | Defourny, Jean | Aghaie, Asadollah | Beurg, Maryline | Dulon, Didier | Thelen, Nicolas | Perfettini, Isabelle | Zelles, Tibor | Aller, Mate | Meyer, Anaïs | Emptoz, Alice | Giraudet, Fabrice | Leibovici, Michel | Dartevelle, Sylvie | Soubigou, Guillaume | Thiry, Marc | Vizi, E Sylvester | Safieddine, Saaid | Hardelin, Jean-Pierre | Avan, Paul | Petit, Christine

Edité par CCSD ; Elsevier -

International audience. 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.

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