Compartmentalization is a fundamental design principle of eukaryotic metabolism. Here, we
review the compartmentalization of NAD+/NADH and NADP+/NADPH with a focus on the
liver, an organ that experiences the extremes of biochemical physiology each day. Historical
studies of the liver, using classical biochemical fractionation and measurements of redox-
coupled metabolites, have given rise to the prevailing view that mitochondrial NAD (H) pools
tend to be oxidized and important for energy homeostasis, whereas cytosolic NADP (H) …