Cells constantly adapt their metabolic pathways to meet their energy needs and respond to nutrient availability. During the last two decades, it has become increasingly clear that NAD+
, a coenzyme in redox reactions, also mediates several ubiquitous cell signaling processes. Protein ADP-ribosylation is a post-translational modification that uses NAD+
as a substrate and is best known as part of the genotoxic stress response. However, there is increasing evidence that NAD+
-dependent ADP-ribosylation regulates other cellular processes, including metabolic pathways. In this review, we will describe the compartmentalized regulation of NAD+
biosynthesis, consumption, and regeneration with a particular focus on the role of ADP-ribosylation in the regulation of glucose metabolism in different cellular compartments.
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