AUTHOR=Holmgren Melanie , Sheets Lavinia TITLE=Influence of Mpv17 on Hair-Cell Mitochondrial Homeostasis, Synapse Integrity, and Vulnerability to Damage in the Zebrafish Lateral Line JOURNAL=Frontiers in Cellular Neuroscience VOLUME=15 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.693375 DOI=10.3389/fncel.2021.693375 ISSN=1662-5102 ABSTRACT=

Noise exposure is particularly stressful to hair-cell mitochondria, which must produce enough energy to meet high metabolic demands as well as regulate local intracellular Ca2+ concentrations. Mitochondrial Inner Membrane Protein 17 (Mpv17) functions as a non-selective cation channel and plays a role in maintaining mitochondrial homeostasis. In zebrafish, hair cells in mpv17a9/a9 mutants displayed elevated levels of reactive oxygen species (ROS), elevated mitochondrial calcium, hyperpolarized transmembrane potential, and greater vulnerability to neomycin, indicating impaired mitochondrial function. Using a strong water current to overstimulate hair cells in the zebrafish lateral line, we observed mpv17a9/a9 mutant hair cells were more vulnerable to morphological disruption than wild type (WT) siblings simultaneously exposed to the same stimulus. To determine the role of mitochondrial homeostasis on hair-cell synapse integrity, we surveyed synapse number in mpv17a9/a9 mutants and WT siblings as well as the sizes of presynaptic dense bodies (ribbons) and postsynaptic densities immediately following stimulus exposure. We observed mechanically injured mpv17a9/a9 neuromasts were not more vulnerable to synapse loss; they lost a similar number of synapses per hair cell relative to WT. Additionally, we quantified the size of hair cell pre- and postsynaptic structures following stimulation and observed significantly enlarged WT postsynaptic densities, yet relatively little change in the size of mpv17a9/a9 postsynaptic densities following stimulation. These results suggest chronically impaired hair-cell mitochondrial activity influences postsynaptic size under homeostatic conditions but does not exacerbate synapse loss following mechanical injury.