The role of mitochondria in rheumatic diseases

The mitochondrion is an intracellular organelle thought to originate from endosymbiosis between an ancestral eukaryotic cell and an alpha-proteobacterium. Mitochondria are the powerhouses of the cell, and can control several important processes within the cell, such as cell death. Conversely, dysregulation of mitochondria possibly contributes to the pathophysiology of several autoimmune diseases. Defects in mitochondria can be caused by mutations in the mitochondrial genome or by chronic exposure to pro-inflammatory cytokines, including type I interferons. Following the release of intact mitochondria or mitochondrial components into the cytosol or the extracellular space, the bacteria-like molecular motifs of mitochondria can elicit pro-inflammatory responses by the innate immune system. Moreover, antibodies can target mitochondria in autoimmune diseases, suggesting an interplay between the adaptive immune system and mitochondria. In this Review, we discuss the roles of mitochondria in rheumatic diseases such as systemic lupus erythematosus, antiphospholipid syndrome and rheumatoid arthritis. An understanding of the different contributions of mitochondria to distinct rheumatic diseases or manifestations could permit the development of novel therapeutic strategies and the use of mitochondria-derived biomarkers to inform pathogenesis. The mitochondrion has multiple functions, including energy production, regulation of apoptosis and reactive oxygen species generation. Disruption of these mitochondrial processes can lead to pro-inflammatory immune responses. This Review discussions the role of mitochondria and mitochondrial dysfunction in rheumatic diseases.

Automated summary

Mitochondria play crucial roles in rheumatic diseases, and understanding their functions and dysfunctions can lead to novel therapeutic strategies.