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

Abstract

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‐κB (NF)‐κB‐ 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 α, Shigella infection and double‐stranded RNA, resulting in amplified NF‐κB‐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.