Cell
Volume 163, Issue 4, 5 November 2015, Pages 894-906
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Article
Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

https://doi.org/10.1016/j.cell.2015.10.023Get rights and content
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Highlights

  • Pejvakin-deficient mice and humans are hypervulnerable to sound exposure

  • Oxidative stress induces a pejvakin-dependent proliferation of peroxisomes

  • Peroxisome proliferation contributes to the physiological response to sound exposure

  • Pjvk gene transfer can rescue auditory dysfunction in Pjvk−/− mice

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.

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