Abstract
Cells utilize a diverse repertoire of cell surface and intracellular receptors to detect exogenous or endogenous danger signals and even the changes of their microenvironment. However, some cytosolic NOD-like receptors (NLR), including NLRX1, serve more functions than just being general pattern recognition receptors. The dynamic translocation between the cytosol and the mitochondria allows NLRX1 to interact with many molecules and thereby to control multiple cellular functions. As a regulatory NLR, NLRX1 fine-tunes inflammatory signaling cascades, regulates mitochondria-associated functions, and controls metabolism, autophagy and cell death. Nevertheless, literature data are inconsistent and often contradictory regarding its effects on individual cellular functions. One plausible explanation might be that the regulatory effects of NLRX1 are highly cell type specific and the features of NLRX1 mediated regulation might be determined by the unique functional activity or metabolic profile of the given cell type. Here we review the cell type specific actions of NLRX1 with a special focus on cells of the immune system. NLRX1 has already emerged as a potential therapeutic target in numerous immune-related diseases, thus we aim to highlight which regulatory properties of NLRX1 are manifested in disease-associated dominant immune cells that presumably offer promising therapeutic solutions to treat these disorders.
Highlights
Based on the extensive and diverse literature data, it is not deniable that nucleotide-binding domain and leucine-rich repeat–containing protein X1 (NLRX1) acting as a Swiss army knife is one of the most multifunctional receptor of mammalian cells
We wish to emphasize that NLRX1 affects basic cellular functions, such as cytokine secretion, mitochondrial reactive oxygen species (mtROS) production, metabolism, autophagy or cell death, which actions can be attributed to almost every cell types
It seems that the major function of NLRX1 is to ensure protective, negative feedback mechanisms to prevent overzealous inflammatory reactions by inhibiting those cellular functions, which might drastically perturb the homeostasis of a given cell type
Summary
Cells of the innate immune system utilize a vast repertoire of evolutionary conserved pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), C-type lectin receptors (CLRs), retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) to detect various microbial motifs or danger signals [1]. They play a central role in the initiation of host defense during the early stages of infection and subsequently contribute to the generation of adaptive immune responses as well [2]. 22 NLRs have been identified in humans, and at least 34 in mice [3]
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