Multi-omics Reveal that c-Src Modulates the Mitochondrial Phosphotyrosine Proteome and Metabolism According to Nutrient Availability.
Animals
Brain
/ metabolism
Chromatography, Liquid
Citric Acid Cycle
/ genetics
Gas Chromatography-Mass Spectrometry
Glycolysis
/ genetics
Kidney
/ metabolism
Mice
Mice, Knockout
Mitochondria
/ enzymology
Mitochondria, Liver
/ genetics
Nutrients
/ metabolism
Phosphorylation
Phosphotyrosine
/ genetics
Proteome
/ metabolism
Proteomics
Tandem Mass Spectrometry
src-Family Kinases
/ genetics
Mitochondria; c-Src kinase; Metabolism; NDUFA8; Nutrient availability; Phosphoproteomics
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
20 May 2020
20 May 2020
Historique:
accepted:
29
04
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
13
1
2021
Statut:
ppublish
Résumé
Src kinase family members, including c-Src, are involved in numerous signaling pathways and have been observed inside different cellular compartments. Notably, c-Src modulates carbohydrate and fatty acid metabolism and is involved in the metabolic rewiring of cancer cells. This kinase is found within mitochondria where it targets different proteins to impact on the organelle functions and overall metabolism. Surprisingly, no global metabolic characterization of Src has been performed although c-Src knock-out mice have been available for 30 years. Considering that c-Src is sensitive to various metabolites, c-Src might represent a crucial player in metabolic adjustments induced by nutrient stress. The aim of this work was to characterize the impact of c-Src on mitochondrial activity and overall metabolism using multi-omic characterization. Src We observed that deletion of c-Src is linked to lower phosphorylation of Y412-NDUFA8, inhibition of oxygen consumption and accumulation of metabolites involved in glycolysis, TCA cycle and amino acid metabolism in mice fed ad libitum. Finally, metabolomics and (phosphotyrosine) proteomics are differently impacted by Src according to nutrient availability. The findings presented here highlight that c-Src reduces mitochondrial metabolism and impacts the metabolic adjustment induced by nutrient stress.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Src kinase family members, including c-Src, are involved in numerous signaling pathways and have been observed inside different cellular compartments. Notably, c-Src modulates carbohydrate and fatty acid metabolism and is involved in the metabolic rewiring of cancer cells. This kinase is found within mitochondria where it targets different proteins to impact on the organelle functions and overall metabolism. Surprisingly, no global metabolic characterization of Src has been performed although c-Src knock-out mice have been available for 30 years. Considering that c-Src is sensitive to various metabolites, c-Src might represent a crucial player in metabolic adjustments induced by nutrient stress. The aim of this work was to characterize the impact of c-Src on mitochondrial activity and overall metabolism using multi-omic characterization.
METHODS
METHODS
Src
RESULTS
RESULTS
We observed that deletion of c-Src is linked to lower phosphorylation of Y412-NDUFA8, inhibition of oxygen consumption and accumulation of metabolites involved in glycolysis, TCA cycle and amino acid metabolism in mice fed ad libitum. Finally, metabolomics and (phosphotyrosine) proteomics are differently impacted by Src according to nutrient availability.
CONCLUSION
CONCLUSIONS
The findings presented here highlight that c-Src reduces mitochondrial metabolism and impacts the metabolic adjustment induced by nutrient stress.
Substances chimiques
Proteome
0
Phosphotyrosine
21820-51-9
src-Family Kinases
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-537Subventions
Organisme : Canadian Cancer Society
ID : 2015-317342
Pays : Canada
Organisme : Natural Sciences and Engineering Research Council of Canada (NSERC)
ID : RGPIN-2015-05880, RGPIN-2017-05100
Pays : Canada
Organisme : Canadian Health Research Institute (CIHR)
ID : 388808
Pays : Canada
Organisme : New Brunswick Health Research Foundation (NBHRF)
Pays : Canada
Organisme : New Brunswick Innovation Foundation (NBIF)
Pays : Canada
Organisme : Université de Moncton
Pays : Canada
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare.