Location, Location, Location: Compartmentalization of NAD+ Synthesis and Functions in Mammalian Cells

Trends Biochem Sci. 2020 Oct;45(10):858-873. doi: 10.1016/j.tibs.2020.05.010. Epub 2020 Jun 25.


The numerous biological roles of NAD+ are organized and coordinated via its compartmentalization within cells. The spatial and temporal partitioning of this intermediary metabolite is intrinsic to understanding the impact of NAD+ on cellular signaling and metabolism. We review evidence supporting the compartmentalization of steady-state NAD+ levels in cells, as well as how the modulation of NAD+ synthesis dynamically regulates signaling by controlling subcellular NAD+ concentrations. We further discuss potential benefits to the cell of compartmentalizing NAD+, and methods for measuring subcellular NAD+ levels.

Keywords: CD38; nicotinamide mononucleotide adenylyltransferase (NMNAT); nicotinamide phosphoribosyltransferase (NAMPT); poly(ADP-ribose) polymerase (PARP); sirtuin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Compartmentation*
  • NAD / biosynthesis
  • NAD / metabolism*
  • Signal Transduction
  • Subcellular Fractions / metabolism*


  • NAD