SIRT3, a nicotinamide adenine dinucleotide (NAD+)-dependent mitochondrial deacetylase, is involved in multiple crucial cellular processes. It plays a positive role in energy metabolism, mitochondrial biogenesis, and protection against oxidative stress. SIRT3 is also associated with pathways related to cell-signaling, heterochromatin regulation, and metabolic reprogramming, which are vital for maintaining cellular homeostasis and organismal health [1,2]. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, Sirt3 deficiency has shown diverse effects. In female mice, Sirt3 deletion accelerates ovarian aging, as indicated by reduced offspring sizes, follicle reserve, and oocyte markers, along with increased aging and inflammation-related gene expression [4]. In male mice, however, Sirt3 -/- shows no significant changes in testicular histology, germ-cell proliferation, and differentiation [4]. In post-traumatic osteoarthritis mouse models, global SIRT3 deletion accelerates pathological phenotypes like cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization [3].

In conclusion, SIRT3 is essential for maintaining mitochondrial function, energy metabolism, and cellular homeostasis. Through model-based research, especially KO mouse models, we've learned that SIRT3 plays a critical role in ovarian senescence and osteoarthritis progression. These findings suggest SIRT3 could be a potential therapeutic target for treating age-related ovarian decline and osteoarthritis [3,4].

References:

1. Zhou, Lei, Pinho, Ricardo, Gu, Yaodong, Radak, Zsolt. 2022. The Role of SIRT3 in Exercise and Aging. In Cells, 11, . doi:10.3390/cells11162596. https://pubmed.ncbi.nlm.nih.gov/36010672/

2. Diao, Zhiqing, Ji, Qianzhao, Wu, Zeming, Song, Moshi, Qu, Jing. . SIRT3 consolidates heterochromatin and counteracts senescence. In Nucleic acids research, 49, 4203-4219. doi:10.1093/nar/gkab161. https://pubmed.ncbi.nlm.nih.gov/33706382/

3. Zhang, Yijian, Liu, Yang, Hou, Mingzhuang, He, Fan, Zhu, Xuesong. 2023. Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3-COX4I2 Axis Attenuates Osteoarthritis Progression. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2206144. doi:10.1002/advs.202206144. https://pubmed.ncbi.nlm.nih.gov/36683245/

4. Zhu, Jing, Yang, Qingling, Li, Hui, Lei, Min, Sun, Yingpu. 2022. Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice. In Free radical biology & medicine, 193, 511-525. doi:10.1016/j.freeradbiomed.2022.10.324. https://pubmed.ncbi.nlm.nih.gov/36336229/