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

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.

Mitochondrial form and function in hair cells

“…In the zebrafish lateral line, the fusion/fission state is less clear in some published electron micrographs ( Dow et al, 2018 ;Laurà et al, 2018 ), with otherwise highly informative live imaging experiments lacking sufficient spatial resolution to provide further clarity on this specific issue ( Pickett et al, 2018 ). However, unpublished work specifically investigating mitochondrial morphology in the zebrafish lateral line HCs using SBF-SEM has revealed that apical mitochondria are smaller and more discrete, whilst those at the base of the cell form a larger reticular network ( McQuate et al, 2022 ). Disruption of network architecture results in a reduced mitochondrial response to mechanical stimulation of the HC.…”