Figure 2. Metabolic reprogramming of differentiating stem cells.
A. In undifferentiated pluripotent stem cells, UCP2 is activated by phosphatidylinositol phosphates (PIPs) at the inner mitochondrial membrane (IMM), which prevents entry of pyruvate into the TCA cycle. Glucose is consequently shunted into alternate metabolic pathways such as the pentose phosphate pathway (PPP). B. During differentiation, the mitochondrial phosphatase PTPMT1 dephosphorylates PIPs, downregulating UCP2 and allowing pyruvate to be metabolized by the TCA cycle to fuel OXPHOS.