Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells

Abstract
Data availability
Article and author information
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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.

The following data sets were generated

(2023) 03052021_WT_left_2
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/03052021_WT_left_2/view#4743,4995,263,0,1.3
(2023) 03052021_WT_SO1_Right
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/03052021_WT_SO1_Right/view#4925,5724,246,0,1.3
(2023) 03052021_WT_SO2_Right
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/03052021_WT_SO2_Right/view#4774,5185,341,0,1.3
(2023) 02102020_WT_6dpf_Right_3
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/02102020_WT_6dpf_Right_3/view#4930,5395,267,0,1.3
(2023) 02102020_WT_6dpf
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/02102020_WT_6dpf/view#4947,5529,222,0,1.3
(2023) 02102020_WT_3dpf_C
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/02102020_WT_3dpf_C/view#4953,3852,212,0,1.3
(2023) 02102020_WT_3dpfA_2
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/02102020_WT_3dpfA_2/view#5297,5328,323,0,1.3
(2023) 11262018_Opa1
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/11262018_Opa1/view#3332,3547,205,0,1.3
(2023) 12052019_cdh23_right
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/12052019_cdh23_right/view#4623,4852,195,0,1.3
(2023) 12052019_cdh23_left
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/12052019_cdh23_left/view#5129,5047,160,0,1.3
(2023) 12192019_cdh23_IO3
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/12192019_cdh23_IO3/view#5690,5783,282,0,1.3
(2023) 12192019_cdh23_fA_SO1
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/12192019_cdh23_fA_SO1/view#5232,6593,288,0,1.3
(2023) 07292020_CaV_A_Right
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/07292020_CaV_A_Right/view#5932,6878,248,0,1.3
(2023) 07292020_CaV_A_Left
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/07292020_CaV_A_Left/view#6142,7029,322,0,1.3
(2023) 07292020_CaV_fishB_right
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/07292020_CaV_fishB_right/view#4836,5799,367,0,1.3
(2023) 07302020_cav_fishB_left_1
Webknossos, webknossos.org.

https://webknossos.org/datasets/91969da369e1a848/07302020_cav_fishB_left_1/view#5657,5364,352,0,1.3

Article and author information

Author details

Andrea McQuate

Department of Biological Structure, University of Washington, Seattle, United States

For correspondence
amcquate@uw.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2052-2004
Sharmon Knecht

Department of Biological Structure, University of Washington, Seattle, United States

Competing interests
The authors declare that no competing interests exist.
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.

"This ORCID iD identifies the author of this article:" 0000-0002-5342-5841

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

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.