Metabolic regulation of transcription through compartmentalized NAD⁺ biosynthesis.

ABSTRACT: NAD⁺ (nicotinamide adenine dinucleotide in its oxidized state) is an essential molecule for a variety of physiological processes. It is synthesized in distinct subcellular compartments by three different synthases (NMNAT-1, -2, and -3). We found that compartmentalized NAD⁺ synthesis by NMNATs integrates glucose metabolism and adipogenic transcription during adipocyte differentiation. Adipogenic signaling rapidly induces cytoplasmic NMNAT-2, which competes with nuclear NMNAT-1 for the common substrate, nicotinamide mononucleotide, leading to a precipitous reduction in nuclear NAD⁺ levels. This inhibits the catalytic activity of poly[adenosine diphosphate (ADP)-ribose] polymerase-1 (PARP-1), a NAD⁺-dependent enzyme that represses adipogenic transcr

SUBMITTER: Ryu KW 

PROVIDER: S-EPMC6465534 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature