The potential regulatory roles of NAD(+) and its metabolism in autophagy

(Macro)Autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective Autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of Autophagy are not fully understood. Increasing data indicate that nicotinamide adenine nucleotide (NAD(+)) homeostasis correlates intimately with Autophagy. NAD(+) is a ubiquitous coenzyme that functions primarily as an electron carrier of oxidoreductase in multiple redox reactions. Both NAD(+) homeostasis and its metabolism are thought to play critical roles in regulating Autophagy. In this review, we discuss how the regulation of NAD(+) and its metabolism can influence Autophagy. We focus on the regulation of NAD(+)/NADH homeostasis and the effects of NAD(+) consumption by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1), NAD(+)-dependent deacetylation by sirtuins and NAD(+) metabolites on Autophagy processes and the underlying mechanisms. Future studies should provide more direct evidence for the regulation of Autophagy processes by NAD(+). A better understanding of the critical roles of NAD(+) and its metabolites on Autophagy will shed light on the complexity of Autophagy regulation, which is essential for the discovery of new therapeutic tools for autophagy-related diseases.