NLRX1/NOD5 deficiency does not affect MAVS signalling

Dear Editor,

NLRX1/NOD5 belongs to the NOD clade of the NOD-like receptor (NLR) family. NLRs have emerged as key intracellular sensors for pathogen-derived molecules and endogenous danger signals to activate innate immune responses and inflammation. However, the function of most of these receptors still remains unclear.¹ Beside the NACHT and LRR domains present in most NLRs, NLRX1/NOD5 possesses a N-terminal mitochondrial targeting sequence.^{2, 3} The function of NLRX1/NOD5 is still controversial; one study proposed that NLRX1/NOD5 inhibits the RIG-like receptor (RLR) antiviral pathways by binding the adaptor protein MAVS/IPS-1/Cardif/VISA,² whereas another report implicated NLRX1/NOD5 in the generation of reactive oxygen species (ROS) and the amplification of NF-κB and JNK activation triggered by different stimuli such TNF-α, poly (I:C) and Shigella infection.³ Interestingly, a recent study proposed that NLRX1/NOD5 is imported to the mitochondrial matrix, making NLRX1/NOD5 interaction with the outer mitochondrial membrane protein MAVS difficult to explain.⁴

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