Alteration of mitochondrial proteome due to activation of Notch1 signaling pathway [Genomics and Proteomics]

January 28th, 2014 by Basak, N. P., Roy, A., Banerjee, S.

The Notch signaling pathway, a known regulator of cell fate decisions, proliferation and apoptosis has recently been implicated in the regulation of glycolysis which affects tumor progression. However, the impact of Notch on other metabolic pathways remains to be elucidated. To gain more insights into the Notch signaling and its role in regulation of metabolism we studied the mitochondrial proteome in Notch1 activated K562 cells using a comparative proteomics approach. The proteomic study led to the identification of 10 unique proteins which were altered due to Notch1 activation. Among these 8 proteins belonged to mitochondrially localized metabolic pathways like oxidative phosphorylation, glutamine metabolism, Krebs cycle and fatty acid oxidation. Validation of some of these findings showed that constitutive activation of Notch1 deregulated glutamine metabolism and complex 1 of the respiratory chain. Further, the deregulation of glutamine metabolism involved the canonical Notch signaling and its downstream effectors. The study also reports the effect of Notch signaling on mitochondrial function and status of high energy intermediates ATP, NADH and NADPH. Thus our study shows the effect of Notch signaling on mitochondrial proteome which in turn affects the functioning of key metabolic pathways thereby connecting an important signaling pathway to the regulation of cellular metabolism.