NLRX1

NLRX1 is a member of the NOD-like receptor (NLR) family of intracellular pattern recognition receptors involved in innate immune signaling. It is encoded by the NLRX1 gene and has orthologs across vertebrates. The protein features an N-terminal mitochondrial targeting sequence, a central NACHT (NTPase) domain, and C-terminal leucine-rich repeats. Unlike many other NLRs, it lacks a defined N-terminal effector domain such as PYD or CARD, which contributes to its unique signaling properties and subcellular localization.

Localization to mitochondria is a defining aspect of NLRX1 function. By residing on the mitochondrial membrane, it can influence signaling pathways that converge on mitochondria, including those driven by RIG-I-like receptors and the mitochondrial antiviral signaling (MAVS) adaptor. In this context, NLRX1 is best known for negative regulation of type I interferon responses during RNA virus infection, partially through interaction with MAVS and modulation of RIG-I-like receptor signaling.

Beyond antiviral signaling, NLRX1 is implicated in regulating mitochondrial reactive oxygen species production, autophagy and mitophagy, and broader inflammatory responses. Its effects on inflammation appear to be context dependent, with reports of both suppressive and more complex, stimulus-specific outcomes in different cell types and conditions.

Expression of NLRX1 is relatively broad, with notable levels in immune-related tissues and various other cell types. Because of its involvement in mitochondrial homeostasis and innate immunity, NLRX1 has been studied in infections, cancer biology, and inflammatory diseases, though findings are not yet fully consistent and ongoing work seeks to clarify its precise mechanisms and physiological relevance.