Sirt3pink1pkm2 Axis Prevents Osteoarthritis Via Mitochondrial Renewal And Metabolic Switch Yaoge Deng Mingzhuang Hou Yubin Wu Yang Liu Xiaowei Xia Chenqi Yu Jianfeng Yu Huilin Yang Yijian Zhang Xuesong Zhu by Yaoge Deng & Mingzhuang Hou & Yubin Wu & Yang Liu & Xiaowei Xia & Chenqi Yu & Jianfeng Yu & Huilin Yang & Yijian Zhang & Xuesong Zhu 101038/S41413025004134 instant download after payment.

Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistanceagainst osteoarthritis (OA). However, the underlying mechanisms governing mitochondrial self-renewal and energy productionremain elusive. In this study, we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes. Geneticallyoverexpressing PTEN-induced putative kinase 1 (PINK1) protects against cartilage degeneration by removing defectivemitochondria. PINK1 knockout aggravated cartilage damage due to impaired mitophagy. SIRT3 directly deacetylated PINK1 topromote mitophagy and cartilage anabolism. Specifically, PINK1 phosphorylated PKM2 at the Ser127 site, preserving its activetetrameric form. This inhibited nuclear translocation and the interaction with β-catenin, resulting in a metabolic shift and increasedenergy production. Finally, a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguardingthe structural integrity of articular joints and improving motor functions. Overall, this study provides a novel insight into the1234567890();,:regulation of mitochondrial renewal and metabolic switches in OA.Bone Research (2025) 13:36 ;