FIGURE 1.

Metabolic requirements in pluripotent stem cells and differentiated cells. Most of the quiescent stem cell populations rely on glycolysis to provide ATP and building blocks necessary for the synthesis of lipids, proteins or nucleotides. Along differentiation, energy metabolism shifts toward mitochondrial OXPHOS to support the increasing energy demands. Glycolysis-associated enzymes, such as hexokinase (HK), pyruvate kinase (PK) and lactate dehydrogenase A (LDHA), are highly expressed in PSCs. Pyruvate import into mitochondria is repressed by high expression of uncoupling protein 2 (UCP2). UCP2 is upregulated by accumulation of phosphatidylinositol phosphate (PIP) substrates following the downregulation of the mitochondrial phosphatase PTPMT1. αKG, α-ketoglutarate; ATP, adenosine triphosphate; CS, citrate synthase; G6P, glucose 6-phosphate; HIF, hypoxia-inducible factor; MPC, mitochondrial pyruvate carrier; PDH, pyruvate dehydrogenase; PDK, PDH kinase; OAA, oxaloacetate. Elevated metabolic pathways are indicated with bold arrows.