Mitochondrial CB1 receptors regulate neuronal energy metabolism

被引：414

作者：

Benard, Giovanni ^{[1
,2
,3
]}

Massa, Federico ^{[1
,3
]}

Puente, Nagore ^{[4
]}

Lourenco, Joana ^{[1
,3
,5
]}

Bellocchio, Luigi ^{[1
,3
]}

Soria-Gomez, Edgar ^{[1
,3
]}

Matias, Isabel ^{[1
,3
]}

Delamarre, Anna ^{[1
,3
]}

Metna-Laurent, Mathilde ^{[1
,3
]}

Cannich, Astrid ^{[1
,3
]}

Hebert-Chatelain, Etienne ^{[1
,3
]}

Mulle, Christophe ^{[3
,5
]}

Ortega-Gutierrez, Silvia ^{[6
]}

Martin-Fontecha, Mar ^{[6
]}

Klugmann, Matthias ^{[7
,8
]}

Guggenhuber, Stephan ^{[7
]}

Lutz, Beat ^{[7
]}

Gertsch, Juerg ^{[9
]}

Chaouloff, Francis ^{[1
,3
]}

Lopez-Rodriguez, Maria Luz ^{[6
]}

Grandes, Pedro ^{[4
]}

Rossignol, Rodrigue ^{[2
,3
]}

Marsicano, Giovanni ^{[1
,3
]}

机构：

[1] INSERM, U862, Neuroctr Magendie, Bordeaux, France

[2] Univ Bordeaux, EA 4576, Bordeaux, France

[3] Univ Bordeaux, Neuroctr Magendie, U862, Bordeaux, France

[4] Univ Basque Country, Fac Med & Dent, Dept Neurosci, UPV EHU, Leioa, Spain

[5] Ctr Natl Rech Sci, Lab Physiol Cellulaire Synapse, UMR 5091, Bordeaux, France

[6] Univ Complutense, Dept Organ Chem, E-28040 Madrid, Spain

[7] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Physiol Chem, Mainz, Germany

[8] Univ New S Wales, Sch Med Sci, Dept Physiol, Sydney, NSW, Australia

[9] Inst Biochem & Mol Med, Bern, Switzerland

来源：

NATURE NEUROSCIENCE | 2012年 / 15卷 / 04期

基金：

欧洲研究理事会;

关键词：

CANNABINOID RECEPTOR; COMPLEX-I; ENDOCANNABINOID SYSTEM; PHOSPHORYLATION; PHARMACOLOGY; HIPPOCAMPUS; INHIBITION; TRANSPORT; OXIDASE;

D O I：

10.1038/nn.3053

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 (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 CB1 receptors and mitochondria, 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.

引用

页码：558 / 564

页数：7

共 37 条

[1] A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration [J].