PUBLICATION
Synaptic mitochondria regulate hair-cell synapse size and function
- Authors
- Wong, H.C., Zhang, Q., Beirl, A.J., Petralia, R.S., Wang, Y.X., Kindt, K.
- ID
- ZDB-PUB-191015-14
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Beirl, Alisha, Kindt, Katie, Wong, Hiu-Tung Candy, Zhang, Qiuxiang
- Keywords
- developmental biology, neuroscience, zebrafish
- MeSH Terms
-
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology
- Animals
- Animals, Genetically Modified
- Calcium/metabolism*
- Calcium Channel Agonists/pharmacology
- Calcium Channel Blockers/pharmacology
- Calcium Channels, L-Type/genetics
- Calcium Channels, L-Type/metabolism*
- Calcium Signaling
- Cell Size
- Embryo, Nonmammalian
- Evoked Potentials, Auditory/physiology*
- Eye Proteins/chemistry
- Eye Proteins/genetics
- Eye Proteins/metabolism*
- Gene Expression
- Hair Cells, Auditory/cytology
- Hair Cells, Auditory/drug effects
- Hair Cells, Auditory/metabolism*
- Isradipine/pharmacology
- Mitochondria/drug effects
- Mitochondria/metabolism*
- Mitochondria/ultrastructure
- NAD/metabolism
- Oxidation-Reduction
- Protein Binding
- Protein Interaction Domains and Motifs
- Ruthenium Compounds/pharmacology
- Synapses/drug effects
- Synapses/metabolism*
- Synapses/ultrastructure
- Synaptic Transmission
- Zebrafish
- Zebrafish Proteins/agonists
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 31609202 Full text @ Elife
Citation
Wong, H.C., Zhang, Q., Beirl, A.J., Petralia, R.S., Wang, Y.X., Kindt, K. (2019) Synaptic mitochondria regulate hair-cell synapse size and function. eLIFE. 8:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping