SIRT3, a nicotinamide adenine dinucleotide (NAD+)-dependent mitochondrial deacetylase, plays a crucial role in multiple cellular processes. It positively modulates energy metabolism, mitochondrial biogenesis, and protection against oxidative stress [1]. SIRT3 is also involved in pathways related to cell senescence, macrophage polarization, and tumor suppression, highlighting its overall biological importance. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying SIRT3.

In KO mouse models, SIRT3 deficiency has been shown to have various effects. In female mice, Sirt3 deletion accelerates ovarian aging, as indicated by a decline in offspring sizes, follicle reserve, and oocyte markers, along with increased expression of aging and inflammation-related genes [3]. In post-traumatic osteoarthritis mice, global SIRT3 deletion accelerates pathological phenotypes like cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization [2]. In contrast, male Sirt3 -/- mice show no changes in testicular histology, serum testosterone levels, germ-cell proliferation, and differentiation [3]. Additionally, in Sirt3 -/- mice, more intestinal mucosal cells undergo ferroptosis, and intestinal ischemia-reperfusion injury is more severe [4].

In conclusion, SIRT3 is essential for maintaining cellular homeostasis, with its functions spanning across multiple biological processes. Studies using SIRT3 KO mouse models have revealed its significance in diseases such as ovarian senescence, osteoarthritis, and intestinal ischemia-reperfusion injury. These findings provide valuable insights into potential therapeutic strategies targeting SIRT3 for treating related diseases.