The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways.
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| Abstract |
A century after the identification of a coenzymatic activity for NAD(+), NAD(+) metabolism has come into the spotlight again due to the potential therapeutic relevance of a set of enzymes whose activity is tightly regulated by the balance between the oxidized and reduced forms of this metabolite. In fact, the actions of NAD(+) have been extended from being an oxidoreductase cofactor for single enzymatic activities to acting as substrate for a wide range of proteins. These include NAD(+)-dependent protein deacetylases, poly(ADP-ribose) polymerases, and transcription factors that affect a large array of cellular functions. Through these effects, NAD(+) provides a direct link between the cellular redox status and the control of signaling and transcriptional events. Of particular interest within the metabolic/endocrine arena are the recent results, which indicate that the regulation of these NAD(+)-dependent pathways may have a major contribution to oxidative metabolism and life span extension. In this review, we will provide an integrated view on: 1) the pathways that control NAD(+) production and cycling, as well as its cellular compartmentalization; 2) the signaling and transcriptional pathways controlled by NAD(+); and 3) novel data that show how modulation of NAD(+)-producing and -consuming pathways have a major physiological impact and hold promise for the prevention and treatment of metabolic disease.
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| Authors | Riekelt H Houtkooper, Carles Cantó, Ronald J Wanders, Johan Auwerx |
| Journal | Endocrine reviews (Endocr Rev) Vol. 31 Issue 2 Pg. 194-223 (Apr 2010) ISSN: 1945-7189 [Electronic] United States |
| PMID | 20007326 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review) |
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