Dual control of NAD+ synthesis by purine metabolites in yeast

  1. Benoît Pinson
  2. Johanna Ceschin
  3. Christelle Saint-Marc
  4. Bertrand Daignan-Fornier  Is a corresponding author
  1. Université de Bordeaux IBGC UMR 5095, France

Abstract

Metabolism is a highly integrated process resulting in energy and biomass production. While individual metabolic routes are well characterized, the mechanisms ensuring crosstalk between pathways are poorly described though they are crucial for homeostasis. Here, we establish a co-regulation of purine and pyridine metabolism in response to external adenine through two separable mechanisms. First, adenine depletion promotes transcriptional up-regulation of the de novo NAD+ biosynthesis genes by a mechanism requiring the key-purine intermediates ZMP/SZMP and the Bas1/Pho2 transcription factors. Second, adenine supplementation favors the pyridine salvage route resulting in an ATP-dependent increase of intracellular NAD+. This control operates at the level of the nicotinic acid mononucleotide adenylyl-transferase Nma1 and can be bypassed by overexpressing this enzyme. Therefore, in yeast, pyridine metabolism is under the dual control of ZMP/SZMP and ATP, revealing a much wider regulatory role for these intermediate metabolites in an integrated biosynthesis network.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures and supplemental Figures

The following previously published data sets were used

Article and author information

Author details

  1. Benoît Pinson

    Université de Bordeaux IBGC UMR 5095, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2936-9058
  2. Johanna Ceschin

    Université de Bordeaux IBGC UMR 5095, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Christelle Saint-Marc

    Université de Bordeaux IBGC UMR 5095, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Bertrand Daignan-Fornier

    Université de Bordeaux IBGC UMR 5095, Bordeaux, France
    For correspondence
    b.daignan-fornier@ibgc.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2352-9700

Funding

The authors declare that there was no funding for this work

Reviewing Editor

  1. Alan G Hinnebusch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States

Publication history

  1. Received: November 21, 2018
  2. Accepted: March 11, 2019
  3. Accepted Manuscript published: March 12, 2019 (version 1)
  4. Version of Record published: March 22, 2019 (version 2)

Copyright

© 2019, Pinson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Benoît Pinson
  2. Johanna Ceschin
  3. Christelle Saint-Marc
  4. Bertrand Daignan-Fornier
(2019)
Dual control of NAD+ synthesis by purine metabolites in yeast
eLife 8:e43808.
https://doi.org/10.7554/eLife.43808

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