Nicotinamide phosphoribosyltransferase regulates cell survival through autophagy in cardiomyocytes

Nicotinamide adenine dinucleotide (NAD+) acts as a transfer molecule for electrons, thereby acting as a key cofactor for energy production. NAD+ also serves as a substrate for cellular enzymes, including poly (ADP-ribose) polymerase (PARP)-1 and Sirt1. Activation of PARP-1 by DNA damage depletes the cellular pool of NAD+, leading to necrotic cell death. NAD+ in the nucleus enhances the activity of Sirt1, thereby modulating transcription. NAD+ is either synthesized de novo from amino acids, namely tryptophan and aspartic acid, or resynthesized from NAD+ metabolites, such as nicotinamide (NAM), through the salvage pathway. NAM phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the NAD+ salvage pathway. We have recently demonstrated that Nampt is an important regulator of NAD+ and autophagy in cardiomyocytes. Here we discuss the role of Nampt in regulating autophagy and potential mechanisms by which NAD+ regulates autophagy in the heart.