The Pathophysiological Role of Mitochondrial Oxidative Stress in Rheumatic Diseases.

Mitochondria play a crucial role in reactive oxygen species (ROS)-dependent rheumatic diseases, including ankylosing spondylitis, osteoarthritis (OA), systemic lupus erythematosus (SLE) and scleroderma. Mitochondrial DNA (mtDNA), which encodes mitochondrial proteins, is more vulnerable to oxidants compared to nuclear DNA. When mtDNA gets damaged, it leads to mitochondrial dysfunction, such as electron transport chain impairment and loss of mitochondrial membrane potential. Moreover, the damaged mtDNA functions as a damage-associated molecular pattern (DAMP), triggering inflammatory and immune responses. In this review, ROS-related transcription factors and downstream cell signaling pathways are investigated. It also explains the mechanism of mitochondrial dysfunction and the clinical significance of major rheumatic diseases, as well as the clinical transformation status of key antioxidants, the risks/reasons for promoting mitochondrial ROS research in rheumatic diseases, and antioxidant therapy. We conclude that targeting oxidative stress with antioxidant agents,such as polyphenols, garlic, pomegranate, Coenzyme Q10, probiotic, α-lipoic acid, N-acetylcysteine (NAC), selenium, microalgae, fucoidan, resveratrol, quercetin, and curcumin should be considered as promising new strategies for treating rheumatic diseases lacking effective treatments.