NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-κB and JNK pathways by inducing reactive oxygen species production

NOD-like receptors (NLRs) are a family of intracellular sensors of microbial- or danger-associated molecular patterns. Here, we report the identification of NLRX1, which is a new member of the NLR family that localizes to the mitochondria. NLRX1 alone failed to trigger most of the common signalling pathways, including nuclear factor-kappa B (NF)-kappa B- and type I interferon-dependent cascades, but could potently trigger the generation of reactive oxygen species (ROS). Importantly, NLRX1 synergistically potentiated ROS production induced by tumour necrosis factor a, Shigella infection and double-stranded RNA, resulting in amplified NF-kappa B-dependent and JUN amino-terminal kinases-dependent signalling. Together, these results identify NLRX1 as a NLR that contributes to the link between ROS generation at the mitochondria and innate immune responses.