Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells
- University of Washington, United States
Abstract
Mitochondria play a prominent role in mechanosensory hair cell damage and death. Although hair cells are thought to be energetically demanding cells, how mitochondria respond to these demands and how this might relate to cell death is largely unexplored. Using genetically encoded indicators, we found mitochondrial calcium flux and oxidation are regulated by mechanotransduction and demonstrate that hair cell activity has both acute and long-term consequences on mitochondrial function. We tested whether variation in mitochondrial activity reflected differences in vulnerability of hair cells to the toxic drug neomycin. We observed that susceptibility did not correspond to the acute level of mitochondrial activity but rather to the cumulative history of that activity.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute on Deafness and Other Communication Disorders (R01DC015783)
- David W Raible
National Science Foundation (DGE-1256082)
- Sarah B Pickett
National Institute on Deafness and Other Communication Disorders (T32DC536115)
- Sarah B Pickett
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2997-01) of the University of Washington.
Copyright
© 2018, Pickett et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells
eLife 7:e38062.
https://doi.org/10.7554/eLife.38062
