SIRT3, a nicotinamide adenine dinucleotide (NAD+)-dependent mitochondrial deacetylase, plays a crucial role in multiple cellular processes. It is involved in energy metabolism, mitochondrial biogenesis, and protection against oxidative stress. SIRT3 also has links to pathways related to aging, inflammation, and apoptosis [1,2,3]. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In Sirt3 KO mice, ovarian aging was accelerated, as shown by decreased offspring sizes, follicle reserve, and oocyte markers, along with increased aging and inflammation-related gene expression. Oocytes also displayed mitochondrial dysfunction and spindle assembly disruption [5]. In post-traumatic osteoarthritis mouse models, global SIRT3 deletion accelerated the pathological phenotype, including cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization [4]. In addition, Sirt3-deficient mice had more severe intestinal ischemia-reperfusion injury, with increased ferroptosis in intestinal mucosal cells [6].

In conclusion, SIRT3 is essential for maintaining mitochondrial function, cellular redox balance, and plays a significant role in various physiological and pathological processes. The use of Sirt3 KO mouse models has revealed its importance in diseases such as ovarian senescence, osteoarthritis, and intestinal ischemia-reperfusion injury, providing insights into potential therapeutic strategies for these conditions.