Metabolic regulation of redox status in stem cells

Significance: Metabolism-dependent generation of reactive oxygen species (ROS) and associated oxidative damage have been traditionally linked to impaired homeostasis and cellular death. Beyond the adverse effects of ROS accumulation, increasing evidence implicates redox status as a regulator of vital cellular processes. Recent Advances: Emerging studies on the molecular mechanisms guiding stem cell fate decisions indicate a role for energy metabolism in regulating the fundamental ability of maintaining stemness versus undergoing lineage-specific differentiation. Stem cells have evolved protective metabolic phenotypes to minimize reactive oxygen generation through oxidative metabolism and support antioxidant scavenging through glycolysis and the pentose phosphate pathway. Critical Issues: While the dynamics in ROS generation has been correlated with stem cell function, the intimate mechanisms by which energy metabolism regulates ROS to impact cellular fate remain to be deciphered. Future Directions: Decoding the linkage between nutrient sensing, energy metabolism, and ROS in regulating cell fate decisions would offer a redox-dependent strategy to regulate stemness and lineage specification.