Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sarah B Pickett

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Eric D Thomas

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Joy Y Sebe

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tor Linbo

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Esterberg

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dale W Hailey

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. David W Raible

    Department of Biological Structure, University of Washington, Seattle, United States
    For correspondence
    draible@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5342-5841

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.

Reviewing Editor

  1. Dwight E Bergles, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: May 3, 2018
  2. Accepted: December 31, 2018
  3. Accepted Manuscript published: December 31, 2018 (version 1)
  4. Version of Record published: January 24, 2019 (version 2)

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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  1. Sarah B Pickett
  2. Eric D Thomas
  3. Joy Y Sebe
  4. Tor Linbo
  5. Robert Esterberg
  6. Dale W Hailey
  7. David W Raible
(2018)
Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells
eLife 7:e38062.
https://doi.org/10.7554/eLife.38062

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