The Role of Mitochondrial Regulation in Macrophage Polarization: Implications for the Pathogenesis of Rheumatoid Arthritis

Pingshun Li,1,2 Gang Wang,1 Zhihui Peng,3 Lihuan Zhang,1 Fang Yang,1 Yong Wei,1 Meihan Pan,2 Haohao Zang,2 Mengru Zhou1 1Department of Rheumatology and Bone Disease, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 2College of Integrative Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China; 3School of Physical Education and Health, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of ChinaCorrespondence: Mengru Zhou, Email [email protected]: Rheumatoid arthritis (RA) is an autoimmune arthropathy closely associated with chronic inflammation, whose pathogenesis involves macrophages, particularly M1 macrophage-induced inflammatory responses. Mitochondria, as key organelles governing macrophage metabolism and function, regulate M1/M2 macrophage polarization through multiple pathways and signaling molecules, thereby inducing immune and inflammatory responses that contribute to RA development. Therefore, this paper delves into the intricate mechanisms by which mitochondria regulate macrophage-specific polarization. These pathways encompass metabolic processes, signaling molecules, mitochondrial dynamics, mitochondrial-associated molecules, mitochondrial autophagy, ion homeostasis, and mitochondrial translocation. The study underscores the pivotal role of mitochondria in macrophage-specific polarization and highlights the potential for basic research to intervene in RA by modulating Mitochondrial metabolism, mitochondrial dynamics, mitochondrial autophagy, and mitochondrial translocation to promote M1-to-M2 macrophage conversion and suppress RA inflammatory responses. This holds significant implications for repairing RA-induced bone destruction and advancing clinical treatment.Keywords: rheumatoid arthritis, macrophages, M1/M2 polarization, inflammatory response, pathogenesis