Underlying Mechanisms and Related Diseases Behind the Complex Regulatory Role of NOD-Like Receptor X1

Among nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), NOD-like receptor X1 (NLRX1) is the only known NLR family member that is targeted to the mitochondria, which contains a C-terminal leucine-rich repeat domain, a central conserved nucleotide-binding domain, and an unconventional N-terminal effector domain. It is unique due to several atypical features, such as mitochondrial localization, noninflammasome forming, and relatively undefined N-terminal domain. NLRX1 has multiple functions, including negative regulation of type-I interferon signaling, attenuation of proinflammatory nuclear factor kappa B (NF-κB) signaling, autophagy induction, modulation of reactive oxygen species production, cell death regulation, and participating in cellular senescence. In addition, due to its diverse functions, NLRX1 has been associated with various human diseases, including respiratory, circulatory, motor, urinary, nervous, and digestive systems, to name but a few. However, the exact regulatory mechanisms of NLRX1 are still unclear in many related diseases since conflicting and controversial topics on NLRX1 in the previous studies remain. In this review, we review recent research advances on the underlying mechanisms and related disorders behind the complex regulatory role of NLRX1, which may provide a promising target to prevent and/or treat the corresponding diseases.