De novo NAD<sup>+</sup> synthesis enhances mitochondrial function and improves health.

Details

Serval ID
serval:BIB_7236863D4813
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
De novo NAD<sup>+</sup> synthesis enhances mitochondrial function and improves health.
Journal
Nature
Author(s)
Katsyuba E., Mottis A., Zietak M., De Franco F., van der Velpen V., Gariani K., Ryu D., Cialabrini L., Matilainen O., Liscio P., Giacchè N., Stokar-Regenscheit N., Legouis D., de Seigneux S., Ivanisevic J., Raffaelli N., Schoonjans K., Pellicciari R., Auwerx J.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
563
Number
7731
Pages
354-359
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Nicotinamide adenine dinucleotide (NAD <sup>+</sup> ) is a co-substrate for several enzymes, including the sirtuin family of NAD <sup>+</sup> -dependent protein deacylases. Beneficial effects of increased NAD <sup>+</sup> levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD <sup>+</sup> synthesis pathway, controls cellular NAD <sup>+</sup> levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD <sup>+</sup> synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD <sup>+</sup> levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.
Pubmed
Web of science
Create date
05/11/2018 8:44
Last modification date
21/08/2019 5:34
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