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Cell. 2015 Nov 5;163(4):894-906. doi: 10.1016/j.cell.2015.10.023.

Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

Author information

1
Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015 Paris, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France; Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, 75005 Paris, France.
2
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France; Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, 75005 Paris, France; Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, 75012 Paris, France.
3
Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Neurosciences Institute, CHU Pellegrin, 33076 Bordeaux, France.
4
Unit of Cell and Tissue Biology, GIGA-Neurosciences, University of Liege, CHU Sart-Tilman, B36, 4000 Liege, Belgium.
5
Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary.
6
Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary.
7
Laboratoire de Biophysique Sensorielle, Université d'Auvergne, 63000 Clermont-Ferrand, France; UMR 1107, Institut National de la Santé et de la Recherche Médicale (INSERM), 63000 Clermont-Ferrand, France; Centre Jean Perrin, 63000 Clermont-Ferrand, France.
8
Plateforme d'Ingénierie des Anticorps, Institut Pasteur, 75015 Paris, France.
9
Plateforme Transcriptome et Épigénome, Institut Pasteur, 75015 Paris, France.
10
Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015 Paris, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France; Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, 75005 Paris, France; Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, 75012 Paris, France; Collège de France, 75005 Paris, France. Electronic address: christine.petit@pasteur.fr.

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.

PMID:
26544938
DOI:
10.1016/j.cell.2015.10.023
[Indexed for MEDLINE]
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