Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells
- University of Washington, United States
Abstract
Hair cells of the inner ear are particularly sensitive to changes in mitochondria, the subcellular organelles necessary for energy production in all eukaryotic cells. There are over thirty mitochondrial deafness genes, and mitochondria are implicated in hair cell death following noise exposure, aminoglycoside antibiotic exposure, as well as in age-related hearing loss. However, little is known about the basic aspects of hair cell mitochondrial biology. Using hair cells from the zebrafish lateral line as a model and serial block-face scanning electron microscopy, we have quantifiably characterized a unique hair cell mitochondrial phenotype that includes (1) a high mitochondrial volume, and (2) specific mitochondrial architecture: multiple small mitochondria apically, and a reticular mitochondrial network basally. This phenotype develops gradually over the lifetime of the hair cell. Disrupting this mitochondrial phenotype with a mutation in opa1 impacts mitochondrial health and function. While hair cell activity is not required for the high mitochondrial volume, it shapes the mitochondrial architecture, with mechanotransduction necessary for all patterning, and synaptic transmission necessary for development of mitochondrial networks. These results demonstrate the high degree to which hair cells regulate their mitochondria for optimal physiology, and provide new insights into mitochondrial deafness.
Data availability
The SBFSEM data volumes for the sixteen different NMs used in this manuscript, including WT and mutants, are publicly available at webKnossos (http://demo.webknossos.org/), searchable by the dataset name indicated in the relevant source data.
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03052021_WT_left_2Webknossos, webknossos.org.
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03052021_WT_SO1_RightWebknossos, webknossos.org.
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03052021_WT_SO2_RightWebknossos, webknossos.org.
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02102020_WT_6dpfWebknossos, webknossos.org.
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02102020_WT_3dpf_CWebknossos, webknossos.org.
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02102020_WT_3dpfA_2Webknossos, webknossos.org.
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11262018_Opa1Webknossos, webknossos.org.
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12052019_cdh23_rightWebknossos, webknossos.org.
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12052019_cdh23_leftWebknossos, webknossos.org.
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12192019_cdh23_IO3Webknossos, webknossos.org.
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12192019_cdh23_fA_SO1Webknossos, webknossos.org.
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07292020_CaV_A_RightWebknossos, webknossos.org.
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07292020_CaV_A_LeftWebknossos, webknossos.org.
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (RO1DC015783)
- David W Raible
National Institute on Deafness and Other Communication Disorders (F32DC017343)
- Andrea McQuate
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 experiments were done in compliance with the University of Washington Institutional Animal Use and Care Committee (IACUC protocol number 2997-01).
Copyright
© 2023, McQuate 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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Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells
eLife 12:e80468.
https://doi.org/10.7554/eLife.80468
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