Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Pathways
  • Hair Cells, Auditory / metabolism
  • Hair Cells, Auditory / pathology
  • Hearing Loss, Noise-Induced / metabolism*
  • Hearing Loss, Noise-Induced / pathology
  • Humans
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Oxidative Stress
  • Peroxisomes / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*


  • Nerve Tissue Proteins
  • PJVK protein, human
  • Proteins
  • pejvakin protein, mouse

Associated data

  • GEO/GSE72722