title: The potential regulatory roles of NAD(+) and its metabolism in autophagy.
abstract: (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.
authors.affiliation: Institute of Burn Research, Southwest Hospital, Third Military Medical University, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing, PR China, 400038.
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, Southwest Hospital, Third Military Medical University, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing, PR China, 400038.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: Endocrinology Department, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, PR China, 400038.
authors.forename: Jiong-Yu
authors.initials: JY
authors.lastname: Hu
authors.affiliation: Institute of Burn Research, Southwest Hospital, Third Military Medical University, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing, PR China, 400038. Electronic address: yshuangtmmu@163.com.
authors.forename: Yue-Sheng
authors.initials: YS
authors.lastname: Huang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D009243:NAD / Q000378:metabolism* / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases
chemical_list: D009243:NAD; D011065:Poly(ADP-ribose) Polymerases
keywords: Autophagy; Ca(2)(+); NAADP/cADPR/ADPR; NAD(+); NAD(P)(+)/NAD(P)H