Acetyl Coenzyme A: A Central Metabolite and Second Messenger

Acetyl-coenzyme A (acetyl-CoA) is a central metabolic intermediate. The abundance of acetyl-CoA in distinct subcellular compartments reflects the general energetic state of the cell. Moreover, acetyl-CoA concentrations influence the activity or specificity of multiple enzymes, either in an allosteric manner or by altering substrate availability. Finally, by influencing the acetylation profile of several proteins, including histones, acetyl-CoA controls key cellular processes, including energy metabolism, mitosis, and autophagy, both directly and via the epigenetic regulation of gene expression. Thus, acetyl-CoA determines the balance between cellular catabolism and anabolism by simultaneously operating as a metabolic intermediate and as a second messenger. Acetyl-coenzyme A (acetyl-CoA) is a key substrate for anabolic reactions and the sole donor of acetyl groups for protein acetylation. In this review, Kroemer and colleagues discuss how acetyl-CoA dictates the balance between cellular catabolism and anabolism by simultaneously operating as a metabolic intermediate and a second messenger.