Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses

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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

The following data sets were generated

1. Doser R
2. Knight K
3. Deihl E
4. Hoerndli FJ
(2024) Image quantification data for: Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses
Dryad Digital Repository, doi:10.5061/dryad.0gb5mkm71.

https://dx.doi.org/10.5061/dryad.0gb5mkm71

Article and author information

Author details

Rachel L Doser

Department of Biomedical Science, Colorado State University, Fort Collins, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9057-4371
Kaz M Knight

Department of Biomedical Science, Colorado State University, Fort Collins, United States

Competing interests
The authors declare that no competing interests exist.
Ennis W Deihl

Department of Biomedical Science, Colorado State University, Fort Collins, United States

Competing interests
The authors declare that no competing interests exist.
Frederic J Hoerndli

Department of Biomedical Science, Colorado State University, Fort Collins, United States

For correspondence
frederic.hoerndli@colostate.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6838-0386

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

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.