Difference between revisions of "Hebert-Chatelain 2019b MiP2019"

Revision as of 09:06, 7 October 2019

Mitochondria get stoned by cannabinoid receptors.

Link: MiP2019

Hebert-Chatelain E (2019)

Event: MiP2019

Cannabinoid receptors (CB1) are powerful regulators of brain physiology and cognition. These inhibitors of synaptic transmission are activated by exo-cannabinoids (such as the psychoactive THC from Cannabis sativa) and endocannabinoids (that are produced directly in human cells). As other G protein-coupled receptors, CB₁ are classically seen as plasma membrane proteins ideally located to convert extracellular stimuli into intracellular responses. Recent evidence however demonstrated important roles for intracellular CB₁ in higher brain functions. Notably, CB₁ receptors are functionally present in mitochondrial membranes (mtCB₁) in different types of brain cells. Activation of mtCB₁ slows down complex I activity, oxygen consumption and mitochondrial trafficking in several cell types. The impact of mtCB₁ activation on higher brain functions appears however cell type- and brain region- specific. Although it is well known that chronic mitochondrial dysfunctions can lead to neurodegenerative diseases, these novel findings highlight the role of acute modulation of cell type-specific mitochondrial activity in brain physiology and behavior.

• Bioblast editor: Plangger M, Tindle-Solomon L

Labels: MiParea: mt-Structure;fission;fusion

Affiliations

Canada Research Chair in Mitochondrial Signaling and Physiopathology, University of Moncton, Canada

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 {{Abstract
-|title=[[Image:Chatelain EH Photo.JPG|left|120px|Etienne Herbert Chatelain]] Src kinase slows down mitochondrial fission and OXPHOS via phosphorylation of ATP5B.
+|title=[[Image:Chatelain EH Photo.JPG|left|120px|Etienne Herbert Chatelain]] Mitochondria get stoned by cannabinoid receptors.
 |info=[[MiP2019]]
-|authors=Hebert-Chatelain E, Lurette O, Guedouari, Morris J, Prudent J
+|authors=Hebert-Chatelain E
 |year=2019
 |event=MiP2019
 |abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]
-Src kinase is a key player in various signaling pathways and is involved in multiple physiological processes, ranging from metabolism to cellular proliferation, from synaptic transmission to tumorigenesis. For decades, this kinase was thought to reside exclusively in cytosol. Src kinase was however observed within mitochondria more than 15 years ago. Surprisingly, the role and targets of intra-mitochondrial Src kinase (mtSrc) remains scantly studied. The aim of this work is to characterize the functional role and the interactome of mtSrc. We observed that silencing or deletion of Src in different cellular models induces mitochondrial elongation and inhibition of cellular respiration. Expression of Src specifically targeted to mitochondria rescues alterations of mitochondrial shape. Several mtSrc targets were identified using the BioID approach, among which ATP5B-Y418 is involved in both OXPHOS and mitochondrial dynamics. Strikingly, we observed that expression of a mutant of ATP5B mimicking its phosphorylation by mtSrc (ATP5BY418D) reverses mitochondrial alterations observed in Src<sup>-/-</sup> cells. Interestingly, expression of mtSrc or ATP5B-Y418D blunts mitochondrial elongation induced by nutrient deprivation. These results suggest that mtSrc-dependent phosphorylation of ATP5B-Y418 represents a novel key mechanism in the adaptation of mitochondria during stressful conditions.
+Cannabinoid receptors (CB1) are powerful regulators of brain physiology and cognition. These inhibitors of synaptic transmission are activated by exo-cannabinoids (such as the psychoactive THC from ''Cannabis sativa'') and endocannabinoids (that are produced directly in human cells). As other G protein-coupled receptors, CB<sub>1</sub> are classically seen as plasma membrane proteins ideally located to convert extracellular stimuli into intracellular responses. Recent evidence however demonstrated important roles for intracellular CB<sub>1</sub> in higher brain functions. Notably, CB<sub>1</sub> receptors are functionally present in mitochondrial membranes (mtCB<sub>1</sub>) in different types of brain cells. Activation of mtCB<sub>1</sub> slows down complex I activity, oxygen consumption and mitochondrial trafficking in several cell types. The impact of mtCB<sub>1</sub> activation on higher brain functions appears however cell type- and brain region- specific. Although it is well known that chronic mitochondrial dysfunctions can lead to neurodegenerative diseases, these novel findings highlight the role of acute modulation of cell type-specific mitochondrial activity in brain physiology and behavior.
 |editor=[[Plangger M]], [[Tindle-Solomon L]]
 }}
 {{Labeling
-|area=Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression
+|area=mt-Structure;fission;fusion
 }}
 == Affiliations ==
-::::Hebert-Chatelain E(1), Lurette O(1), Guedouari(1), Morris J(2), Prudent J(2)
+::::Canada Research Chair in Mitochondrial Signaling and Physiopathology, University of Moncton, Canada
-::::#Canada Research Chair Mitochondrial Signaling Physiopathology, Dept Biology, Univ Moncton, New Brunswick, Canada
-::::#MRC Mitochondrial Biology Unit, Univ Cambridge, UK. - etienne.hebert.chatelain@umoncton.ca