Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Trends Cell Biol. 2023 Sep;33(9):788-802. doi: 10.1016/j.tcb.2023.02.004. Epub 2023 Mar 5.
Autophagy is an intracellular degradation pathway that recycles subcellular components to maintain metabolic homeostasis. NAD is an essential metabolite that participates in energy metabolism and serves as a substrate for a series of NAD-consuming enzymes (NADases), including PARPs and SIRTs. Declining levels of autophagic activity and NAD represent features of cellular ageing, and consequently enhancing either significantly extends health/lifespan in animals and normalises metabolic activity in cells. Mechanistically, it has been shown that NADases can directly regulate autophagy and mitochondrial quality control. Conversely, autophagy has been shown to preserve NAD levels by modulating cellular stress. In this review we highlight the mechanisms underlying this bidirectional relationship between NAD and autophagy, and the potential therapeutic targets it provides for combatting age-related disease and promoting longevity.
自噬是一种细胞内降解途径，可回收细胞内成分以维持代谢平衡。NAD 是一种必需代谢物，参与能量代谢，并作为一系列消耗 NAD 的酶（NADases）的底物，包括 PARPs 和 SIRTs。自噬活性和 NAD 水平的降低是细胞衰老的特征，因此显著增强这两者都能显著延长动物的健康/寿命并使细胞的代谢活性正常化。从机制上讲，已经表明 NADases 可以直接调节自噬和线粒体质量控制。相反，自噬通过调节细胞应激来维持 NAD 水平。在这篇综述中，我们强调了 NAD 和自噬之间这种双向关系的机制，以及它为对抗与年龄相关的疾病和促进长寿提供的潜在治疗靶点。
