HealthDay News — In patients with systemic lupus erythematosus (SLE), mitochondrial reactive oxygen species (ROS) induce oligomerization of mitochondrial antiviral signaling (MAVS) protein and type I interferon (IFN) production, according to a study published recently in Science Signaling.

Iwona A. Buskiewicz, PhD, from the University of Vermont in Burlington, and colleagues examined virus-independent activation of MAVS protein in patients with SLE.

Noting that MAVS protein usually forms a complex with retinoic acid gene I (RIG-I)-like helicases during viral infection, the researchers found that MAVS protein was activated by oxidative stress, independently of RIG-I helicases. Chemically generated oxidative stress stimulated formation of MAVS oligomers, leading to mitochondrial hyperpolarization and reduced adenosine triphosphate production and spare respiratory capacity; these responses were not seen in cells lacking MAVS that were treated in a similar way. 


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Spontaneous MAVS oligomerization was seen in peripheral blood lymphocytes of SLE patients; this correlated with increased secretion of type I IFN and mitochondrial oxidative stress. MAVS oligomerization and type I IFN production were prevented by inhibition of mitochondrial ROS by the mitochondria-targeted antioxidant MitoQ. In cells expressing the MAVS-C79F variant, which is linked to reduced type I IFN secretion, there was reduced ROS-dependent MAVS oligomerization in plasma versus healthy controls.

“Our findings suggest that oxidative stress-induced MAVS oligomerization in SLE patients may contribute to the type I IFN signature that is characteristic of this syndrome,” the authors wrote.

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Reference

Buskiewicz IA, Montgomery T, Yasewicz EC, et al. Reactive oxygen species induce virus-independent MAVS oligomerization in systemic lupus erythematosus. Sci Signal. 2016;9(456):ra115. doi:10.1126/scisignal.aaf1933