Metabolic and Transcriptomic Reprogramming During Contact Inhibition-Induced Quiescence Is Mediated by YAP-Dependent and YAP-Independent Mechanisms

This study investigates the metabolic changes during the transition from proliferation to quiescence in mouse embryonic fibroblasts (MEFs) induced by contact inhibition. Quiescent (Q) cells show reduced glycolysis but increased TCA cycle flux and mitochondrial respiration. The decrease in glycolytic activity is linked to the inhibition of yes-associated protein (YAP), while the increase in TCA cycle activity is due to elevated mitochondrial pyruvate carrier (MPC) expression, making Q cells susceptible to MPC inhibition. Additionally, Q cells exhibit altered malate and pyruvate fluxes, affecting NADPH production. Transcriptomic analysis reveals that many genes related to the extracellular matrix (ECM) are upregulated in Q cells, whereas YAP-dependent and cell cycle-related genes are downregulated. The findings indicate that enhanced TCA cycle flux and respiration in Q cells are crucial for ATP and amino acid production, supporting ECM protein synthesis and secretion.