title: Mitochondrial CB₁ receptors regulate neuronal energy metabolism.
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 (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.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de plasticité neuronale, Endocannabinoids and Neuroadaptation, U862, Bordeaux, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bénard
authors.forename: Federico
authors.initials: F
authors.lastname: Massa
authors.forename: Nagore
authors.initials: N
authors.lastname: Puente
authors.forename: Joana
authors.initials: J
authors.lastname: Lourenço
authors.forename: Luigi
authors.initials: L
authors.lastname: Bellocchio
authors.forename: Edgar
authors.initials: E
authors.lastname: Soria-Gómez
authors.forename: Isabel
authors.initials: I
authors.lastname: Matias
authors.forename: Anna
authors.initials: A
authors.lastname: Delamarre
authors.forename: Mathilde
authors.initials: M
authors.lastname: Metna-Laurent
authors.forename: Astrid
authors.initials: A
authors.lastname: Cannich
authors.forename: Etienne
authors.initials: E
authors.lastname: Hebert-Chatelain
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.forename: Silvia
authors.initials: S
authors.lastname: Ortega-Gutiérrez
authors.forename: Mar
authors.initials: M
authors.lastname: Martín-Fontecha
authors.forename: Matthias
authors.initials: M
authors.lastname: Klugmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Guggenhuber
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Jürg
authors.initials: J
authors.lastname: Gertsch
authors.forename: Francis
authors.initials: F
authors.lastname: Chaouloff
authors.forename: María Luz
authors.initials: ML
authors.lastname: López-Rodríguez
authors.forename: Pedro
authors.initials: P
authors.lastname: Grandes
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D043884:Receptor, Cannabinoid, CB1