Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy

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 via 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.