Mitochondria in the Pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and inflammation in multiple organs. In this article, we present data on how various mitochondria pathologies are involved in the pathogenesis of the disease including the fact that they serve as a reservoir of autoantigens which contribute to the upending of lymphocyte tolerance.

Mitochondrial DNA from various cell sources, including neutrophil extracellular traps, platelets, and red blood cells, elicits the production of type I interferon which contributes to breaking of peripheral tolerance. Mitochondrial DNA also serves as autoantigen targeted by autoantibodies. Mutations of mitochondrial DNA triggered by reactive oxygen species induce T cell cross-reactivity against self-antigens. Selective gene polymorphisms that regulate mitochondrial apoptosis in autoreactive B and T cells represent another key aspect in the induction of autoimmunity. Various mitochondrial abnormalities, including changes in mitochondrial function, oxidative stress, genetic polymorphism, mitochondrial DNA mutations, and apoptosis pathways, are each linked to different aspects of lupus pathogenesis. However, whether targeting these mitochondrial pathologies can be used to harness autoimmunity remains to be explored.