Rheumatoid Arthritis-associated Depression: Focusing on the Interactions between Mitochondria and Endoplasmic Reticulum

Mingqin Shi¹昕瑶 李¹Haimei Zhou¹Zhenmin Li²Yuanyuan Wei¹Zihui Wang¹Yuqing She¹Xuelian Zou¹Xiangdian Xiao^3*Jiashun Zeng^4*Dongdong Qin^1*

• ¹Yunnan University of Chinese Medicine, Kunming, China
• ²Changchun University of Chinese Medicine, Changchun, Jilin Province, China
• ³Qujing Medical College, Qujing, Yunnan Province, China
• ⁴Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China

The interplay between mitochondria and endoplasmic reticulum (ER) is essential for cellular viability. The structures known as mitochondria-associated endoplasmic reticulum membranes (MAM) provide complicated connections between these organelles, which house a variety of proteins, each serving distinct roles across different cellular environments. Growing evidence indicates that disruptions in mitochondrial-ER interactions are linked to immune and inflammatory responses. The concurrent presence of rheumatoid arthritis (RA), an immune-mediated inflammatory condition, and depression has been well-documented. Alterations in proteins that mediate mitochondrial-ER interactions and MAM functionality are increasingly correlated with immune and inflammatory pathways. This suggests that a comprehensive understanding of disease mechanisms can be enhanced by examining the alterations in their intercommunication rather than viewing the organelles in isolation. In this review, we explore the pathophysiological mechanisms underlying RA in conjunction with depression, the relationships among mitochondria, the endoplasmic reticulum, mitochondrial-ER interactions, and their association with RA-associated depression, and propose that targeting MAM could offer a novel therapeutic approach for managing RA-associated depression.