Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses
Abstract
Our understanding of mitochondrial signaling in the nervous system has been limited by the technical challenge of analyzing mitochondrial function in vivo. In the transparent genetic model Caenorhabditis elegans, we were able to manipulate and measure mitochondrial ROS (reactive oxygen species) signaling of individual mitochondria as well as neuronal activity of single neurons in vivo. Using this approach, we provide evidence supporting a novel role for mitochondrial ROS signaling in dendrites of excitatory glutamatergic C. elegans interneurons. Specifically, we show that following neuronal activity, dendritic mitochondria take up calcium (Ca2+) via the mitochondrial Ca2+ uniporter MCU-1 that results in an upregulation of mitochondrial ROS production. We also observed that mitochondria are positioned in close proximity to synaptic clusters of GLR-1, the C. elegans ortholog of the AMPA subtype of glutamate receptors that mediate neuronal excitation. We show that synaptic recruitment of GLR-1 is upregulated when MCU-1 function is pharmacologically or genetically impaired but is downregulated by mitoROS signaling. Thus, signaling from postsynaptic mitochondria may regulate excitatory synapse function to maintain neuronal homeostasis by preventing excitotoxicity and energy depletion.
Data availability
All data generated or analysed during this study are accessible on DRYAD under the following DOI https://doi.org/10.5061/dryad.0gb5mkm71
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Image quantification data for: Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapsesDryad Digital Repository, doi:10.5061/dryad.0gb5mkm71.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (NS115947)
- Frederic J Hoerndli
College Research Council grant from CVMBS, Colorado State
- Rachel L Doser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Doser et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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