Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness

Abstract Cell metabolism has long been recognized as a fundamental process for energy production, biomolecule synthesis, and cell survival. During transitions between stem and somatic states, central carbon metabolism is rewired with concurrent changes in chromatin regulation and gene expression. Because a specific central carbon metabolic transition occurs simultaneously during the epigenetic transition from stem cells to somatic cells or vice versa, metabolism has an important role in determining the epigenetic landscape that influences cell fate. Oxidoreductases are key enzymes that catalyze oxidation–reduction reactions during central carbon metabolism. They also have important roles in determining the metabolic flux and epigenetic landscapes by supplying epigenetic metabolites, directly shaping chromatin structures through posttranslational modifications, and acting as scaffold proteins for epigenetic complexes to affect chromatin states. In this Review, we outline emerging mechanisms by which oxidoreductases couple metabolic flux to epigenetic landscapes that maintain or dissolve stemness.