Work

Synaptic mitochondria regulate hair-cell synapse size and function

Year: 2019

Type: article

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.

Source: eLife

DOI: 10.7554/elife.48914

Authors: Hiu-tung C. Wong, Qiuxiang Zhang, Alisha J. Beirl, Ronald S. Petralia, Ya-Xian Wang, Katie S. Kindt

Institutions: National Institutes of Health, Johns Hopkins University, National Institute on Deafness and Other Communication Disorders

Language: English

Topic: Hearing, Cochlea, Tinnitus, Genetics

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funders: National Institutes of Health, National Institute on Deafness and Other Communication Disorders