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

Sarah B Pickett1,2, Eric D Thomas1,2, Joy Y Sebe1

  • 1Department of Biological Structure, University of Washington, Seattle, United States.

Elife
|January 1, 2019
PubMed

Insights

Mitochondria in sensory hair cells are affected by mechanical forces. Hair cell vulnerability to toxins depends on the long-term history of mitochondrial activity, not just the immediate level.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Sensory Biology

Background:

  • Mitochondria are crucial for cellular energy and survival.
  • Mechanosensory hair cells are vital for hearing and balance.
  • The role of mitochondria in hair cell mechanotransduction and death is poorly understood.

Purpose of the Study:

  • To investigate mitochondrial responses to mechanotransduction in hair cells.
  • To determine the relationship between mitochondrial activity and hair cell death.

Main Methods:

  • Utilized genetically encoded indicators to monitor mitochondrial calcium flux and oxidation.
  • Assessed hair cell activity and its acute/long-term effects on mitochondrial function.
  • Examined hair cell vulnerability to the toxic drug neomycin in relation to mitochondrial activity.

Main Results:

  • Mitochondrial calcium flux and oxidation are regulated by mechanotransduction.
  • Hair cell activity impacts mitochondrial function both acutely and over the long term.
  • Hair cell susceptibility to neomycin toxicity correlated with the cumulative history of mitochondrial activity, not the acute level.

Conclusions:

  • Mechanotransduction significantly influences mitochondrial dynamics in sensory hair cells.
  • The long-term history of mitochondrial activity is a key determinant of hair cell vulnerability to toxic insults.
  • Understanding these mitochondrial dynamics is crucial for addressing hearing and balance disorders.

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