NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB 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-kappaB (NF)-kappaB- 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 alpha, Shigella infection and double-stranded RNA, resulting in amplified NF-kappaB-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.
Tattoli
Ivan
I
Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Carneiro
Leticia A
LA
Jéhanno
Muguette
M
Magalhaes
Joao G
JG
Shu
Youmin
Y
Philpott
Dana J
DJ
Arnoult
Damien
D
Girardin
Stephen E
SE
D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010802:Phylogeny; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012760:Shigella / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D024101:Mitochondrial Proteins; D016328:NF-kappa B; C527006:NLRX1 protein, human; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases