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 (ADPribose) polymerase (PARP)-1 and Sirtl. 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 Sirtl, 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.