Mitochondrial CB₁ receptors regulate neuronal energy metabolism.

Giovanni Bénard, Federico Massa, Nagore Puente, Joana Lourenço, Luigi Bellocchio, Edgar Soria-Gómez, Isabel Matias, Anna Delamarre, Mathilde Metna-Laurent, Astrid Cannich, Etienne Hebert-Chatelain, Christophe Mulle, Silvia Ortega-Gutiérrez, Mar Martín-Fontecha, Matthias Klugmann, Stephan Guggenhuber, Beat Lutz, Jürg Gertsch, Francis Chaouloff, María Luz López-Rodríguez, Pedro Grandes, Rodrigue Rossignol, Giovanni Marsicano
Nat Neurosci. 2012-03-04; 15(4): 558-564
DOI: 10.1038/nn.3053

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1. Nat Neurosci. 2012 Mar 4;15(4):558-64. doi: 10.1038/nn.3053.

Mitochondrial CB₁ receptors regulate neuronal energy metabolism.

Bénard G(1), 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 ML, Grandes P, Rossignol R, Marsicano G.

Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de plasticité neuronale,
Endocannabinoids and Neuroadaptation, U862, Bordeaux, France.

Comment in
Nat Neurosci. 2012 Apr;15(4):499-501.

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.

DOI: 10.1038/nn.3053
PMID: 22388959 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus