PHGDH and you can PSAT1 knockout hindered the latest TCA years function and you will mitochondrial breathing within the IDH2-higher tissues
Thus, in addition to the improved glycolysis, IDH2 diverts the newest glycolytic intermediates in order to serine and you will glycine synthesis, that’s you’ll need for the brand new bioenergetic consult and you may precursors that service cancer tumors development
To predict the potential metabolic vulnerability of IDH2 we applied GSMM aisle pulpit, incorporating the proteomic data of the IDH2-perturbed cell lines. Constraint-based modeling with the iMAT algorithm computed the most likely metabolic activity in the cells, and the minimization of metabolic adjustment (MOMA) algorithm was then used to predict the protein essentiality only in IDH2-high cells. The MOMA analysis predicted PHGDH, PSAT1, and S-formyl glutathione hydrolase (ESD) as essential proteins for IDH2-induced biomass production, thus forming SDL interactions with IDH2 (Fig. 4A). ادامه مطلب … →