Chen Yinfeng, Wang Ying, Yu Dongrong, Zhao Hailing, Li Ping
Department of Nephrology, TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Ren Fail. 2025 Dec;47(1):2543927. doi: 10.1080/0886022X.2025.2543927. Epub 2025 Aug 19.
Diabetic kidney disease (DKD) is a microvascular complication of diabetes and a major cause of kidney failure; current treatment methods still need improvement. Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase located in the mitochondria, where it regulates the activity and biological functions of diverse proteins and influences various mitochondrial functions deacetylation. Increasing research indicates that SIRT3 holds promise as a therapeutic target for DKD. This review examines SIRT3's impact on mitochondrial functions, including mitochondrial biogenesis, autophagy, dynamics, oxidative homeostasis, and energy metabolism. We summarize that SIRT3 delays the progression of DKD by inhibiting oxidative stress, reducing inflammation, regulating cell death, and modulating energy metabolism. Finally, we categorize the applications of SIRT3 activators in renal diseases. In summary, this review provides a thorough understanding of SIRT3's functional role in DKD and proposes a potential therapeutic approach pending clinical validation.
糖尿病肾病(DKD)是糖尿病的一种微血管并发症,也是肾衰竭的主要原因;目前的治疗方法仍需改进。沉默调节蛋白3(SIRT3)是一种位于线粒体中的烟酰胺腺嘌呤二核苷酸(NAD+)依赖性蛋白脱乙酰酶,它在其中调节多种蛋白质的活性和生物学功能,并影响各种线粒体功能的去乙酰化作用。越来越多的研究表明,SIRT3有望成为DKD的治疗靶点。本文综述了SIRT3对线粒体功能的影响,包括线粒体生物发生、自噬、动力学、氧化稳态和能量代谢。我们总结认为,SIRT3通过抑制氧化应激、减轻炎症、调节细胞死亡和调节能量代谢来延缓DKD的进展。最后,我们对SIRT3激活剂在肾脏疾病中的应用进行了分类。总之,本文全面阐述了SIRT3在DKD中的功能作用,并提出了一种有待临床验证的潜在治疗方法。