Journal
CELL METABOLISM
Volume 33, Issue 6, Pages 1076-1087Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2021.04.003
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Funding
- Helen Diller Family Foundation
- Ted Nash Long Life Foundation
- Glenn Foundation for Medical Research via the Paul F. Glenn Laboratories for the Biology of Aging at the Mayo Clinic
- Calico Life Sciences
- Noaber Foundation
- NIH National Institute on Aging (NIA) [AG26094, AG58812, CA233790]
- Mayo Foundation
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NAD and NADP have diverse roles beyond co-factors in oxidation-reduction reactions, including signaling pathways, post-translational modifications, epigenetic changes, and RNA regulation. Recent studies have shown that NAD metabolism is highly dynamic with a short halflife in some tissues, and new concepts are emerging in the roles of NAD pathway metabolites in various disease states. Resolving open questions in NAD biology will lead to significant advancements in the field.
NAD(H) and NADP(H) have traditionally been viewed as co-factors (or co-enzymes) involved in a myriad of oxidation-reduction reactions including the electron transport in the mitochondria. However, NAD pathway metabolites have many other important functions, including roles in signaling pathways, post-translational modifications, epigenetic changes, and regulation of RNA stability and function via NAD-capping of RNA. Non-oxidative reactions ultimately lead to the net catabolism of these nucleotides, indicating that NAD metabolism is an extremely dynamic process. In fact, recent studies have clearly demonstrated that NAD has a halflife in the order of minutes in some tissues. Several evolving concepts on the metabolism, transport, and roles of these NAD pathway metabolites in disease states such as cancer, neurodegeneration, and aging have emerged in just the last few years. In this perspective, we discuss key recent discoveries and changing concepts in NAD metabolism and biology that are reshaping the field. In addition, we will pose some open questions in NAD biology, including why NAD metabolism is so fast and dynamic in some tissues, how NAD and its precursors are transported to cells and organelles, and how NAD metabolism is integrated with inflammation and senescence. Resolving these questions will lead to significant advancements in the field.
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