Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
Molecular Metabolism. 2014-07-01; 3(4): 495-504
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1. Mol Metab. 2014 Apr 2;3(4):495-504. doi: 10.1016/j.molmet.2014.03.007.
eCollection 2014 Jul.
Cannabinoid control of brain bioenergetics: Exploring the subcellular
localization of the CB1 receptor.
Hebert-Chatelain E(1), Reguero L(2), Puente N(2), Lutz B(3), Chaouloff F(1),
Rossignol R(4), Piazza PV(1), Benard G(1), Grandes P(2), Marsicano G(1).
(1)INSERM U862, NeuroCentre Magendie, 33077 Bordeaux, France ; University of
Bordeaux, 33077 Bordeaux, France.
(2)Department of Neurosciences, Faculty of Medicine and Dentistry, University of
the Basque Country UPV/EHU, 48940 Leioa, Spain.
(3)Institute of Physiological Chemistry, University Medical Center of the
Johannes Gutenberg University, Mainz, Germany.
(4)University of Bordeaux, 33077 Bordeaux, France ; Laboratoire Maladies Rares:
Génétique et Métabolisme, 33077 Bordeaux, France.
Brain mitochondrial activity is centrally involved in the central control of
energy balance. When studying mitochondrial functions in the brain, however,
discrepant results might be obtained, depending on the experimental approaches.
For instance, immunostaining experiments and biochemical isolation of organelles
expose investigators to risks of false positive and/or false negative results. As
an example, the functional presence of cannabinoid type 1 (CB1) receptors on
brain mitochondrial membranes (mtCB1) was recently reported and rapidly
challenged, claiming that the original observation was likely due to artifact
results. Here, we addressed this issue by directly comparing the procedures used
in the two studies. Our results show that the use of appropriate controls and
quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and
that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists
reliably decrease respiration in brain mitochondria. These data further underline
the importance of adapted experimental procedures to study brain mitochondrial