Mitochondrial CB₁ receptors regulate neuronal energy metabolism

Bénard, Giovanni; Massa, Federico; Puente, Nagore; Lourenço, Joana; Bellocchio, Luigi; Soria-Gómez, Edgar; Matias, Isabel; Delamarre, Anna; Metna-Laurent, Mathilde; Cannich, Astrid; Hebert-Chatelain, Etienne; Mulle, Christophe; Ortega-Gutiérrez, Silvia; Martín-Fontecha, Mar; Klugmann, Matthias; Guggenhuber, Stephan; Lutz, Beat; Gertsch, Jürg; Chaouloff, Francis; López-Rodríguez, María Luz; ... (2012). Mitochondrial CB₁ receptors regulate neuronal energy metabolism. Nature neuroscience, 15(4), pp. 558-64. New York, N.Y.: Nature America 10.1038/nn.3053

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Gertsch, Jürg

ISSN:

1097-6256

Publisher:

Nature America

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:38

Last Modified:

17 Mar 2015 21:30

Publisher DOI:

10.1038/nn.3053

PubMed ID:

22388959

Web of Science ID:

000302114500015

URI:

https://boris.unibe.ch/id/eprint/15268 (FactScience: 222571)

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