Alteration of mitochondrial proteome due to activation of Notch1 signaling pathway.
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 that were altered due to Notch1 activation. Eight of these proteins belonged to mitochondria-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. Furthermore, 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.
From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
Nandini Pal
NP
Basak
Anita
A
Roy
Subrata
S
Banerjee
D000818:Animals; D002470:Cell Survival; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010100:Oxygen / Q000737:chemistry; D020543:Proteome; D040901:Proteomics; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction
D005227:Fatty Acids; C497761:NOTCH1 protein, human; D020543:Proteome; D051881:Receptor, Notch1; D005973:Glutamine; D042967:Electron Transport Complex I; D010100:Oxygen
Complex 1; Glutamine; Mitochondria; Notch Pathway; Proteomics; Respiratory Chain