SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch.

ABSTRACT: Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis (OA). However, the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive. In this study, we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes. Genetically overexpressing PTEN-induced putative kinase 1 (PINK1) protects against cartilage degeneration by removing defective mitochondria. PINK1 knockout aggravated cartilage damage due to impaired mitophagy. SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism. Specifically, PINK1 phosphorylated PKM2 at the Ser127 site, preserving its active tetrameric form. This inhibited nuclear translocation and the in

SUBMITTER: Deng Y 

PROVIDER: S-EPMC11909255 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature