RRC ID 48722
Author Fujimoto C, Iwasaki S, Urata S, Morishita H, Sakamaki Y, Fujioka M, Kondo K, Mizushima N, Yamasoba T.
Title Autophagy is essential for hearing in mice.
Journal Cell Death Dis
Abstract Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and their damage is the major cause of hearing loss. There is no measurable HC regeneration in the mammalian cochlea, and the maintenance of cell function is crucial for preservation of hearing. Here we generated mice deficient in autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5 resulted in HC degeneration and profound congenital hearing loss. In autophagy-deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate, accumulated as inclusion bodies during the first postnatal week, and these aggregates increased in number. These findings revealed that basal autophagy has an important role in maintenance of HC morphology and hearing acuity.
Volume 8(5)
Pages e2780
Published 2017-5-11
DOI 10.1038/cddis.2017.194
PII cddis2017194
PMID 28492547
PMC PMC5520715
MeSH Animals Autophagy / physiology* Autophagy-Related Protein 5 / genetics Autophagy-Related Protein 5 / metabolism* Gene Deletion Hair Cells, Auditory / cytology Hair Cells, Auditory / metabolism* Hearing / physiology* Mice Mice, Transgenic Sequestosome-1 Protein / genetics Sequestosome-1 Protein / metabolism
IF 6.304
Times Cited 15
Mice RBRC00806