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 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.
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, New Jersey, USA.
Chiao-Po
CP
Hsu
Nirmala
N
Hariharan
Ralph R
RR
Alcendor
Shinichi
S
Oka
Junichi
J
Sadoshima
D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D002470:Cell Survival; D004579:Electron Transport; D006801:Humans; D051379:Mice; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*
D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase