Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses
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 reactive oxygen species (mitoROS)...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/92376 |
| _version_ | 1827294349881245696 |
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| author | Rachel L Doser Kaz M Knight Ennis W Deihl Frederic J Hoerndli |
| author_facet | Rachel L Doser Kaz M Knight Ennis W Deihl Frederic J Hoerndli |
| author_sort | Rachel L Doser |
| collection | DOAJ |
| description | 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 reactive oxygen species (mitoROS) 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 mitoROS 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 mitoROS 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. |
| first_indexed | 2024-04-24T13:58:29Z |
| format | Article |
| id | doaj.art-fc1339337c274e029099f2ab6ad42094 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-24T13:58:29Z |
| publishDate | 2024-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fc1339337c274e029099f2ab6ad420942024-04-03T16:24:57ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011310.7554/eLife.92376Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapsesRachel L Doser0https://orcid.org/0000-0001-9057-4371Kaz M Knight1https://orcid.org/0000-0002-3184-3620Ennis W Deihl2https://orcid.org/0009-0003-6737-8964Frederic J Hoerndli3https://orcid.org/0000-0001-6838-0386Department of Biomedical Science, Colorado State University, Fort Collins, United States; Department of Health and Exercise Sciences, Colorado State University, Fort Collins, United StatesDepartment of Biomedical Science, Colorado State University, Fort Collins, United States; Cellular and Molecular Biology Graduate Program, Colorado State University, Fort Collins, United StatesDepartment of Biomedical Science, Colorado State University, Fort Collins, United StatesDepartment of Biomedical Science, Colorado State University, Fort Collins, United StatesOur 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 reactive oxygen species (mitoROS) 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 mitoROS 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 mitoROS 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.https://elifesciences.org/articles/92376glutamatesynapsetransportmitochondriaconfocal microscopyreactive oxygen species |
| spellingShingle | Rachel L Doser Kaz M Knight Ennis W Deihl Frederic J Hoerndli Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses eLife glutamate synapse transport mitochondria confocal microscopy reactive oxygen species |
| title | Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses |
| title_full | Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses |
| title_fullStr | Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses |
| title_full_unstemmed | Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses |
| title_short | Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses |
| title_sort | activity dependent mitochondrial ros signaling regulates recruitment of glutamate receptors to synapses |
| topic | glutamate synapse transport mitochondria confocal microscopy reactive oxygen species |
| url | https://elifesciences.org/articles/92376 |
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