title: Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
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.
authors.affiliation: 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.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Delmaghani
authors.affiliation: 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.
authors.forename: Jean
authors.initials: J
authors.lastname: Defourny
authors.affiliation: 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.
authors.forename: Asadollah
authors.initials: A
authors.lastname: Aghaie
authors.affiliation: Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Neurosciences Institute, CHU Pellegrin, 33076 Bordeaux, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Beurg
authors.affiliation: Equipe Neurophysiologie de la Synapse Auditive, Université de Bordeaux, Neurosciences Institute, CHU Pellegrin, 33076 Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Dulon
authors.affiliation: Unit of Cell and Tissue Biology, GIGA-Neurosciences, University of Liege, CHU Sart-Tilman, B36, 4000 Liege, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thelen
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Zelles
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary.
authors.forename: Mate
authors.initials: M
authors.lastname: Aller
authors.affiliation: 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.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Meyer
authors.affiliation: 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.
authors.forename: Alice
authors.initials: A
authors.lastname: Emptoz
authors.affiliation: 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.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Giraudet
authors.affiliation: 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.
authors.forename: Michel
authors.initials: M
authors.lastname: Leibovici
authors.affiliation: Plateforme d'Ingénierie des Anticorps, Institut Pasteur, 75015 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dartevelle
authors.affiliation: Plateforme Transcriptome et Épigénome, Institut Pasteur, 75015 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Soubigou
authors.affiliation: Unit of Cell and Tissue Biology, GIGA-Neurosciences, University of Liege, CHU Sart-Tilman, B36, 4000 Liege, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary.
authors.forename: E Sylvester
authors.initials: ES
authors.lastname: Vizi
authors.affiliation: 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.
authors.forename: Saaid
authors.initials: S
authors.lastname: Safieddine
authors.affiliation: 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.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Avan
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000818:Animals; D001306:Auditory Pathways; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D000094524:Gasdermins
chemical_list: D009419:Nerve Tissue Proteins; D011506:Proteins; C519847:PJVK protein, human; D000094524:Gasdermins; C000605138:pejvakin protein, mouse