Mitochondrial aberrations in systemic lupus erythematosus pathogenesis: Insights and therapeutic implications

Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems. Hallmarks of SLE include elevated type I interferons and autoantibody production, though the exact causes of SLE remain elusive despite advances in research techniques. Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods. Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression. Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations, oxidative stress, immune metabolic reprogramming, and cellular death. These factors collectively contribute to the loss of self‐tolerance, increased autoantibody production, and impaired clearance of immune complexes, leading to their deposition. This triggers sustained inflammatory responses and damages multiple organs. This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE. Targeting mitochondrial pathways presents a promising strategy for treating SLE, potentially improving prognosis and quality of life for those affected. Future research should further investigate the role of mitochondria in the onset and progression of SLE, providing new avenues for understanding and managing this complex disease. Mitochondrial abnormalities are crucial in the progression of systemic lupus erythematosus (SLE), with key elements like mitochondrial DNA mutations, oxidative stress, and immune metabolic reprogramming leading to cellular death. These dysfunctions result in an array of SLE symptoms, pointing toward mitochondrial pathways as potential therapeutic targets for improved patient outcomes. Key points Mitochondrial abnormalities, including DNA mutations, oxidative stress, and immune metabolic reprogramming, play a significant role in the development and progression of systemic lupus erythematosus by contributing to increased autoantibody production and impaired clearance of immune complexes. Emerging treatments that target mitochondrial pathways, such as antioxidant therapies and metabolic interventions, show promise in enhancing current treatment modalities for systemic lupus erythematosus.