Hebert-Chatelain 2012 Biochim Biophys Acta

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Hebert-Chatelain E, Jose C, Gutierrez Cortes N, Dupuy JW, Rocher C, Dachary-Prigent J, Letellier T (2012) Preservation of NADH ubiquinone-oxidoreductase activity by Src kinase-mediated phosphorylation of NDUFB10. Biochim Biophys Acta 1817:718-725.

» PMID: 22321370

Hebert-Chatelain E, Jose C, Gutierrez Cortes N, Dupuy JW, Rocher C, Dachary-Prigent J, Letellier T (2012) Biochim Biophys Acta

Abstract: The tyrosine kinase Src is upregulated in several cancer cells. In such cells, there is a metabolic reprogramming elevating aerobic glycolysis that seems partly dependent on Src activation. Src kinase was recently shown to be targeted to mitochondria where it modulates mitochondrial bioenergetics in non-proliferative tissues and cells. The main goal of our study was to determine if increased Src kinase activity could also influence mitochondrial metabolism in cancer cells (143B and DU145 cells). We have shown that 143B and DU145 cells produce most of the ATP through glycolysis but also that the inhibition of OXPHOS led to a significant decrease in proliferation which was not due to a decrease in the total ATP levels. These results indicate that a more important role for mitochondria in cancer cells could be ensuring mitochondrial functions other than ATP production. This study is the first to show a putative influence of intramitochondrial Src kinase on oxidative phosphorylation in cancer cells. Indeed, we have shown that Src kinase inhibition led to a decrease in mitochondrial respiration via a specific decrease in complex I activities (NADH-ubiquinone oxidoreductase). This decrease is associated with a lower phosphorylation of the complex I subunit NDUFB10. These results suggest that the preservation of complex I function by mitochondrial Src kinase could be important in the development of the overall phenotype of cancer.

Keywords: 143B and DU145 cells, Tyrosine kinase Src, Aerobic glycolysis, Complex I subunit NDUFB10

O2k-Network Lab: FR Bordeaux Letellier T

Labels: Pathology: Cancer 

Organism: Human 

Enzyme: Complex I  Regulation: ATP, ATP production  Coupling state: OXPHOS 

HRR: Oxygraph-2k