Mitochondrial CB1 receptors regulate neuronal energy metabolism
Open accessAbstract
The mammalian brain is one of the organs with the highest energy demands, and mitochondria are key determinants of its functions. Here we show that the type-1 cannabinoid receptor (CB(1)) is present at the membranes of mouse neuronal mitochondria (mtCB(1)), where it directly controls cellular respiration and energy production. Through activation of mtCB(1) receptors, exogenous cannabinoids and in situ endocannabinoids decreased cyclic AMP concentration, protein kinase A activity, complex I enzymatic activity and respiration in neuronal mitochondria. In addition, intracellular CB(1) receptors and mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization-induced suppression of inhibition in the hippocampus. Thus, mtCB(1) receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein-coupled receptor signaling in the brain.
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CB1 receptors are expressed in the mitochondrial membrane, where they act on the regulation of energy metabolism and mitochondrial functions.
“Importantly, CB1 receptors have been shown to be expressed in the mitochondrial membrane, where they act on the regulation of energy metabolism and mitochondrial functions25–27.”
CB1 receptors are expressed in mitochondria where they regulate energy metabolism and mitochondrial functions.
“Recently, CB1 receptors were shown to be expressed in mitochondria where they regulate energy metabolism and mitochondrial functions25–27.”
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References 48 · Cited by 588
- Authors
- Bénard, G., Massa, F., Puente, N., Lourenço, J., Bellocchio, L., Soria-Gómez, E., Matias, I., Delamarre, A., Metna-Laurent, M., Cannich, A., Hebert-Chatelain, E., Mulle, C., Ortega-Gutiérrez, S., Martín-Fontecha, M., Klugmann, M., Guggenhuber, S., Lutz, B., Gertsch, J., Chaouloff, F., López-Rodríguez, M. L., Grandes, P., Rossignol, R., & Marsicano, G.
- Affiliations
- Inserm (FR)
- Université de Bordeaux (FR)
- University of the Basque Country (ES)
- Centre National de la Recherche Scientifique (FR)
- UNSW Sydney (AU)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- University of Bern (CH)
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Marsicano, Giovanni
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2012-03-04
- Volume
- 15
- Issue
- 4
- Pages
- 558-564
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2027642569
- Cited by
- 588
- References
- 48
- Citations by year
- 2026: 29 · 2025: 49 · 2024: 43 · 2023: 44 · 2022: 68 · 2021: 70 · 2020: 51 · 2019: 37 · 2018: 37 · 2017: 45 · 2016: 30 · 2015: 32 · 2014: 26 · 2013: 11 · 2012: 16
- FWCI
- 19.96
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CB1 receptor, neuronal energy metabolism, cellular respiration, endocannabinoids, cyclic AMP, protein kinase A, complex I, hippocampus, synaptic plasticity, depolarization-induced suppression of inhibition, G protein-coupled receptor signaling, brain energy demand
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Cricetulus, Energy Metabolism, Female, Cricetinae, Male, Mitochondria, Neurons, CHO Cells, Mice, Knockout, Receptor, Cannabinoid, CB1, Mitochondrial Membranes, Mice, Rats
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