Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.
Cell. 2015-11-01; 163(4): 894-906
DOI: 10.1016/j.cell.2015.10.023
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1. 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.
Delmaghani S(1), Defourny J(1), Aghaie A(2), Beurg M(3), Dulon D(3), Thelen N(4),
Perfettini I(1), Zelles T(5), Aller M(6), Meyer A(1), Emptoz A(1), Giraudet F(7),
Leibovici M(1), Dartevelle S(8), Soubigou G(9), Thiry M(4), Vizi ES(6),
Safieddine S(1), Hardelin JP(1), Avan P(7), Petit C(10).
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: .
Comment in
Cell. 2015 Nov 5;163(4):790-1.
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cell.2015.10.023
PMID: 26544938 [Indexed for MEDLINE]