6533b82ffe1ef96bd12951ea
RESEARCH PRODUCT
Mitochondrial CB1 receptors regulate neuronal energy metabolism
Francis ChaouloffFrancis ChaouloffChristophe MulleChristophe MulleIsabel MatiasIsabel MatiasAstrid CannichAstrid CannichSilvia Ortega-gutiérrezMatthias KlugmannMatthias KlugmannMathilde Metna-laurentMathilde Metna-laurentNagore PuenteLuigi BellocchioLuigi BellocchioStephan GuggenhuberEdgar Soria-gomezEdgar Soria-gomezPedro GrandesGiovanni BenardBeat LutzRodrigue RossignolGiovanni MarsicanoGiovanni MarsicanoMar Martín-fontechaFederico MassaFederico MassaAnna DelamarreAnna DelamarreJoana LourençoJürg GertschEtienne Hebert-chatelainEtienne Hebert-chatelainMaría L. López-rodríguezsubject
0303 health sciencesCannabinoid receptorCellular respirationGeneral Neurosciencemedicine.medical_treatmentBiologyMitochondrion7. Clean energyEndocannabinoid system3. Good healthCell biology03 medical and health sciences0302 clinical medicinenervous systemMechanism of actionmedicineCannabinoidmedicine.symptomReceptor030217 neurology & neurosurgeryIntracellular030304 developmental biologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-03-04 | Nature Neuroscience |