Interplay between compartmentalized NAD+ synthesis and consumption: A focus on the PARP family

Research output: Contribution to journalReview article

4 Scopus citations

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for redox enzymes, but also moonlights as a substrate for signaling enzymes. When used as a substrate by signaling enzymes, it is consumed, necessitating the recycling of NAD+ consumption products (i.e., nicotinamide) via a salvage pathway in order to maintain NAD+ homeostasis. A major family of NAD+ consumers in mammalian cells are poly-ADP-ribose-polymerases (PARPs). PARPs comprise a family of 17 enzymes in humans, 16 of which catalyze the transfer of ADP-ribose from NAD+ to macromolecular targets (namely, proteins, but also DNA and RNA). Because PARPs and the NAD+ biosynthetic enzymes are subcellularly localized, an emerging concept is that the activity of PARPs and other NAD+ consumers are regulated in a compartmentalized manner. In this review, I discussNAD+ metabolism, how different subcellular pools of NAD+ are established and regulated, and how free NAD+ levels can control signaling by PARPs and redox metabolism.

Original languageEnglish (US)
Pages (from-to)254-262
Number of pages9
JournalGenes and Development
Volume34
Issue number5
DOIs
StatePublished - Mar 1 2020

Keywords

  • ADP-ribosylation
  • Biosensor
  • NAD
  • NAD consumer
  • PARP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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