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Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lpr mice.

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Fortner, Karen A 
Buskiewicz, Iwona 
Huang, Nick 
Gibson, Pamela C 


OBJECTIVES: Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants. METHODS: Lupus-prone MRL-lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function. RESULTS: MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody . CONCLUSIONS: These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus.



T cells, autoimmune diseases, inflammation, systemic lupus erythematosus, Animals, Autoantibodies, Disease Models, Animal, Extracellular Traps, Female, Humans, Interferon Type I, Kidney, Kidney Diseases, Lupus Erythematosus, Systemic, Male, Mice, Mice, Inbred MRL lpr, Mitochondria, Neutrophils, Organophosphorus Compounds, Oxidation-Reduction, Oxidative Stress, Reactive Oxygen Species, T-Lymphocytes, Ubiquinone

Journal Title

Lupus Sci Med

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Medical Research Council (MC_U105663142)
Wellcome Trust (110159/Z/15/Z)