Role of mitochondrial dysfunction in the pathogenesis of rheumatoid arthritis: Looking closely at fibroblast- like synoviocytes

Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease that primarily targets the joints, leading to cartilage and bone destruction. Fibroblast-like synoviocytes (FLS) are specialized cells of the synovial lining in the joint that plays a fundamental role in the development of RA. Particularly, FLS of RA patients (RA-FLS) in the joint exhibit specific characteristics like higher invading and immunogenic properties, hyperproliferation, and reduced apoptotic capacity, suggesting a dysfunctional mitochondrial pool in these cells. Mitochondria are emerging as a potential organelle that can decide cellular immunometabolism, invasion properties, and cell death. Accordingly, multiple studies established that mitochondria are crucial in establishing RA. However, the underlying mechanism of impaired mitochondrial function in RA remains poorly understood. This review will provide an overview of the mitochondrial role in the progression of RA, specifically in the context of FLS biology. We will also outline how mitochondria-centric therapeutics can be achieved that would yield novel avenues of research in pathological mediation and prevention.