The Role of Sirt3 in Kidney Health and Disease

Sirtuin 3 (sirt3), a mitochondrial NAD⁺-dependent deacetylase, is an important enzyme in the maintenance of kidney functions, with critical roles in renal homeostasis, attenuation of oxidative stress, and preservation of mitochondrial homeostasis. This review aims to summarize the current literature on the mechanisms by which sirt3 impacts kidney health and disease, as well as highlight the therapeutic implications of sirt3 targeting. We conducted a PubMed search using the title word "sirt3" and the keyword "kidney" to generate our literature review sources. The animal studies that are explored in this review include cisplatin-induced acute kidney injury, cadmium-induced kidney injury, cecal ligation and puncture (CLP) and lipopolysaccharide-induced sepsis, diabetic kidney fibrosis, high-fat induced kidney disease, and ischemic kidney injury. Increasing evidence points towards a deficiency in sirt3 being an aggravator of mitochondrial dysfunction, promoting abnormal glycolysis, and contributing to the progression of diabetic kidney disease, renal fibrosis, and acute kidney injury. In contrast, pharmacological and dietary activation of sirt3 has been observed to enhance mitochondrial biogenesis, mitigate production of reactive oxygen species (ROS), and preserve the integrity of renal tubular cells under stressful conditions. Collectively, studies point towards sirt3 as a central metabolic and antioxidant regulator within the kidney, and link chronic kidney disease, as well as age-related decline in kidney function, to this enzyme. The conclusion of this review identifies future directions for translational research regarding sirt3 and NAD⁺-dependent regulation of mitochondrial homeostasis in renal medicine.