From NAD+ metabolism to skeletal muscle function: The emerging role of ADP-ribosylation.

Nicotinamide adenine dinucleotide (NAD+) is a metabolic coenzyme and substrate for enzymes catalyzing post-translational modifications such as ADP-ribosylation. This reversible modification, mediated by ADP-ribosyltransferases and hydrolases, regulates cellular processes. Although studied in cancer and DNA repair, its roles in skeletal muscle remain less defined. Emerging evidence shows ADP-ribosylation modifies structural proteins like actin and desmin, affecting filament organization, contractility, and calcium signaling. It contributes to muscle regeneration by regulating satellite cell activation and differentiation, with ARTC1 implicated in myogenesis. Additionally, ADP-ribosylation intersects with insulin signaling, glycolysis, and mitochondrial function, linking it to systemic metabolism and exercise performance. Roles in extracellular matrix interactions suggest involvement in force transmission and remodeling. Advances in proteomics enable identification of ADP-ribosylation targets, offering insight into functional impact. This review aims to compile studies on ADP-ribosylation in skeletal muscle to enhance our comprehension of these mechanisms, potentially revealing new therapeutic opportunities for metabolic and skeletal muscle diseases.