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bioRxiv · 10.1101/671701

Synaptic mitochondria are critical for hair-cell synapse formation and function

Wong, H.-t.·Zhang, Q.·Beirl, A.·Petralia, R.·Wang, Y.-X.·Kindt, K.
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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 formation. Direct application of NAD+ or NADH increases or decreases ribbon formation 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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Wong, H.-t., Zhang, Q., Beirl, A., Petralia, R., Wang, Y.-X., Kindt, K.. 2019-06-14. Synaptic mitochondria are critical for hair-cell synapse formation and function. https://doi.org/10.1101/671701

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