Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

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

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60 Citations (Scopus)


Summary 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.

Original languageEnglish
Pages (from-to)894-906
Number of pages13
Issue number4
Publication statusPublished - Nov 5 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Delmaghani, S., Defourny, J., Aghaie, A., Beurg, M., Dulon, D., Thelen, N., Perfettini, I., Zelles, T., Aller, M., Meyer, A., Emptoz, A., Giraudet, F., Leibovici, M., Dartevelle, S., Soubigou, G., Thiry, M., Vizi, E. S., Safieddine, S., Hardelin, J. P., ... Petit, C. (2015). Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes. Cell, 163(4), 894-906. https://doi.org/10.1016/j.cell.2015.10.023