Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

Delmaghani, S. and Defourny, J. and Aghaie, A. and Beurg, M. and Dulon, D. and Zelles, Tibor and Vizi, E. Szilveszter (2015) Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes. CELL, 163 (4). pp. 894-906. ISSN 0092-8674

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Abstract

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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