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Focusing on the Cell Type Specific Regulatory Actions of NLRX1

Journal

Publisher

MDPI
DOI: 10.3390/ijms22031316

Keywords

NLRX1; regulation; immune cells; myeloid cells; lymphoid cells; antiviral immunity; NF-κ B pathway; autophagy; mitochondria; metabolism

Funding

  1. National Research, Development and Innovation Office (NKFIH) [FK 128294, PD 135193, K 131844, GINOP-2.3.2-15-2016-00050]
  2. European Union
  3. European Regional Development Fund
  4. New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [UNKP-20-05-DE-3]
  5. Hungarian Academy of Sciences

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NLRX1 is a regulatory NOD-like receptor that fine-tunes inflammatory signaling cascades, regulates metabolism, autophagy, and cell death. Its effects may be highly cell type-specific, and further research is needed to clarify its impact on different cellular functions.
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.

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