Regulation of mitochondrial networks in hair cells of the zebrafish lateral line

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PROJECT SUMMARY Hearing impairments resulting from inner ear dysfunction have limited treatment options and no permanent solution. Within the inner ear, hair cells of the cochlea are particularly sensitive to outside insult and genetic perturbations. The high metabolic demand on hair cells suggests they might be vulnerable to alterations in their mitochondria. The current proposal seeks to evaluate the characteristics of mitochondria within hair cells, with an overall hypothesis that hair cells maintain a unique mitochondrial phenotype to fit their metabolic demand. The proposal uses hair cells of the zebrafish lateral line as a model system for hair cells in the inner ear. Through this project, I have shown that lateral line hair cell mitochondria have a unique phenotype, with smaller mitochondria at the apical end of the cell, and reticular networks at the base, near the synaptic ribbons. The project also tested whether this mitochondrial network was specific to hair cells, what genes are involved in maintaining this phenotype, and if it is regulated by mechanotransduction. These approaches to studying mitochondria are novel in that they seek to study mitochondrial dynamics (1) quantitatively, when most previous studies to date rely on subjective classifications and (2) in three dimensions. The results of this proposal will provide new insights into what hair cells require to maintain their efficacy, and how changes in subcellular structures could result in hearing impairment or loss.