Hebert-Chatelain 2019 MiP2019

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Etienne Herbert Chatelain
Src kinase slows down mitochondrial fission and OXPHOS via phosphorylation of ATP5B.

Link: MiP2019

Hebert-Chatelain E, Lurette O, Guedouari, Morris J, Prudent J (2019)

Event: MiP2019

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-/- 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.


Bioblast editor: Plangger M, Tindle-Solomon L


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression 







Affiliations

Hebert-Chatelain E(1), Lurette O(1), Guedouari(1), Morris J(2), Prudent J(2)
  1. Canada Research Chair Mitochondrial Signaling Physiopathology, Dept Biology, Univ Moncton, New Brunswick, Canada
  2. MRC Mitochondrial Biology Unit, Univ Cambridge, UK. - etienne.hebert.chatelain@umoncton.ca