Role of NAD+and mitochondrial sirtuins in cardiac and renal diseases.
The coenzyme nicotinamide adenine dinucleotide (NAD+) has key roles in the regulation of redox status and energy metabolism. NAD+depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD+repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD+enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD+functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD+-dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD+supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD+metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD+-boosting therapies in preclinical animal models. We surmise that modulating the NAD+-sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, 300 N Duke Street, Durham, North Carolina 27701, USA.
Kathleen A
KA
Hershberger
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, 300 N Duke Street, Durham, North Carolina 27701, USA.
Angelical S
AS
Martin
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, 300 N Duke Street, Durham, North Carolina 27701, USA.
Matthew D
MD
Hirschey
D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology; D006331:Heart Diseases / Q000209:etiology*; D006801:Humans; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000209:etiology*; D008928:Mitochondria / Q000502:physiology*; D009243:NAD / Q000502:physiology*; D010084:Oxidation-Reduction; D015398:Signal Transduction; D037761:Sirtuins / Q000502:physiology*
D009243:NAD; D037761:Sirtuins