Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3-COX4I2 Axis Attenuates Osteoarthritis Progression.
Adv Sci (Weinh)
; 10(10): e2206144, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36683245
ABSTRACT
Mitochondrial homeostasis is of great importance for cartilage integrity and associated with the progression of osteoarthritis (OA); however, the underlying mechanisms are unknown. This study aims to investigate the role of mitochondrial deacetylation reaction and investigate the mechanistic relationship OA development. Silent mating type information regulation 2 homolog 3 (SIRT3) expression has a negative correlation with the severity of OA in both human arthritic cartilage and mice inflammatory chondrocytes. Global SIRT3 deletion accelerates pathological phenotype in post-traumatic OA mice, as evidenced by cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization. Mechanistically, SIRT3 prevents OA progression by targeting and deacetylating cytochrome c oxidase subunit 4 isoform 2 (COX4I2) to maintain mitochondrial homeostasis at the post-translational level. The activation of SIRT3 by honokiol restores cartilage metabolic equilibrium and protects mice from the development of post-traumatic OA. Collectively, the loss of mitochondrial SIRT3 is essential for the development of OA, whereas SIRT3-mediated proteins deacetylation of COX4I2 rescues OA-impaired mitochondrial respiratory chain functions to improve the OA phenotype. Herein, the induction of SIRT3 provides a novel therapeutic candidate for OA treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoartritis
/
Sirtuina 3
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2023
Tipo del documento:
Article
País de afiliación:
China