Dual control of NAD+ synthesis by purine metabolites in yeast
- 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
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Effect of AICAR and SAICAR accumulation on global transcriptionNCBI Gene Expression Omnibus, GSE13275.
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Effect of AICAR monophosphate and AICAr riboside accumulation on global transcriptionNCBI Gene Expression Omnibus, GSE29324.
Article and author information
Author details
Bertrand Daignan-Fornier
Funding
The authors declare that there was no funding for this work
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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Dual control of NAD+ synthesis by purine metabolites in yeast
eLife 8:e43808.
https://doi.org/10.7554/eLife.43808
