www.jcb.org/cgi/doi/10.1083/jcb.201207019 JCB 205 JCB: Feature

ribose) polymerase. Nicotinamide adenine dinucleotide (NAD) is a metabolite that was first identified over 100 years ago. At that time, Nobel laureate Sir Arthur Harden discovered a molecular fraction involved in yeast fermentation that he called “cozymase. ” Sub-sequent work of, among others, three additional Nobel laureates, notably Otto Warburg, led to the identification of NAD+ as an essential cofactor of many biochemical reactions either in its oxidized (NAD+) or reduced (NADH) form (Berger et al., 2004; Houtkooper et al., 2010a). For instance, NAD+ is used as a cofactor in glucose and fat breakdown, whereas NADH is used as a substrate for the electron transport chain (Fig. 1). NAD+ precursors have been used extensively as dietary supplements: nicotinic acid (NA; also known as niacin) and nicotinamide (NAM) have been long used to treat pellagra, a niacin deficienc