Synaptic mitochondria regulate hair-cell synapse size and function
- National Institute on Deafness and Other Communication Disorders, National Institutes of Health, United States
Abstract
Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD+/NADH redox and downregulates ribbon size. Direct application of NAD+ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.
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Funding
National Institute on Deafness and Other Communication Disorders (1ZIADC000085-01)
- Hiu-tung C Wong
- Qiuxiang Zhang
- Alisha J Beirl
- Katie Kindt
National Institute on Deafness and Other Communication Disorders (ZICDC000081)
- Ronald S Petralia
- Ya-Xian Wang
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 husbandry and experiments were approved by the NIH Animal Care and Use program under protocol #1362-13.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Synaptic mitochondria regulate hair-cell synapse size and function
eLife 8:e48914.
https://doi.org/10.7554/eLife.48914
