학술논문
Mitochondrial CB1 receptors regulate neuronal energy metabolism.
Document Type
Article
Author
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
Source
Subject
*MAMMAL anatomy
*BRAIN research
*MITOCHONDRIAL RNA
*NEUROLOGY
*METABOLISM
*LABORATORY mice
*CANNABINOIDS
*CYCLIC-AMP-dependent protein kinase
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Language
ISSN
1097-6256
Abstract
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 (CB1) is present at the membranes of mouse neuronal mitochondria (mtCB1), where it directly controls cellular respiration and energy production. Through activation of mtCB1 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 CB1 receptors and mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization-induced suppression of inhibition in the hippocampus. Thus, mtCB1 receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein-coupled receptor signaling in the brain. [ABSTRACT FROM AUTHOR]