NLRX1

Official Full Name

NLR family member X1

Organism

Homo sapiens

GeneID

79671

Background

The protein encoded by this gene is a member of the NLR family and localizes to the outer mitochondrial membrane. The encoded protein is a regulator of mitochondrial antivirus responses. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2013]

Synonyms

NOD5; NOD9; NOD26; DLNB26; CLR11.3;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

The human NLRX1 gene is located on chromosome 11 and encodes 108 amino acids. It has a very high conservation function and plays an important role in identifying pathogenic microorganisms. NRLX1 is a member of the NLR family. Unlike the structure of other members, the nitrogen end of NRLX1 contains a mitochondrial localization sequence, which makes it the first NLR to localize to mitochondria. It has no nitrogen terminal effector domain and is replaced by a mitochondrial targeting sequence of 39 amino acid residues, so that NRLX1 is located in the outer mitochondrial membrane and plays an important role in the directional transmission of mitochondria.

In the human body, NLRX1 is mainly distributed in various tissues and cells of the human body, especially in high-energy and strong-metabolized tissues such as muscle, heart, and breast. Its distribution characteristics also indicate that it is closely related to mitochondrial energy metabolism. There is some controversy about the localization of NLRX1 in the cell. Some scholars believe that NLRX1 is localized on the outer mitochondrial membrane and interacts with MAVS to form a complex, and is localized on the mitochondrial membrane matrix, which is closely related to the intimal respiratory chain complex III.

Figure 1. NLRX1 silencing alters mitochondrial function and negatively regulates TNF-α induced autophagy flux in breast cancer cells. (Singh K., et al. 2019)

Functions of NLRX1

NLRX1 is an immunoregulatory molecule. Innate immunity can identify the early stages of pathogenic microorganisms invading the body and induce the body to produce an adaptive immune response process. It mainly uses TLRs to identify pathogen-related molecular patterns (Pathogen-assased molds, PAmps) and LRR to identify damage-related molecular patterns (DamagesApplicate). The activation of IFN-I, including IFNβ, IFN-α and IFFNω, further induces the expression of related genes through interferon receptors, thereby regulating the processes of cell metabolism, nutrition, and decay, and directly clearing pathogens, further forming immune memory. Animal experiments have shown that NLRX1 is a candidate regulator of mucosal inflammation, metabolism and intestinal microbiome interactions during inflammatory bowel disease (IBD).

NLRX1 plays a positive role in regulating immunity. Through overexpression regulation, it can promote the rapid generation of ROS. Under the stimulation of certain microorganisms, NLRX1 can promote the production of ROS. As a secondary signaling molecule of inflammatory and immune responses, ROS plays an important role in the body's innate immunity process against invading pathogens. Studies have shown that low-level ROS plays an important regulatory role in signal transduction, gene expression regulation, and host defense. For example, NLRX1 accelerates cisplatin-induced ototoxicity in HEI-OC1 cells by promoting ROS production and activation of the JNK signaling pathway.

NLRX1 and Tumor

When tumor cells are present in the body, high levels of ROS and continuous activation of the NF-κB signaling pathway often occur. When high levels of ROS appear in tumor tissues with low oxygen levels, the energy consumption is accelerated, which is a specific manifestation of rapid proliferation of tumor cells. In addition, NLRX1 can also activate Caspas-8 to enhance the role of TNF-α to promote the occurrence of apoptosis. When TNF-α is produced, NLRX1 promotes the production of pre-apoptotic complex II and activates Caspar-8, and promotes ROS generation through mitochondrial respiratory chain complexes I and III, which changes the tumor living environment and inhibits the growth of somatic tumors. In non-viral-infected neurodegenerative diseases, such as Huntington's disease, NLRX1 can also readjust cell outcomes by promoting mitochondrial swelling and lysis, preventing them from turning from necrosis to apoptosis. NLRX1 inhibits the expression of Snail1 in the epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells (HCC) by reducing the phosphorylation of Akt, and induces cancer cell senescence through the Akt-P21 dependent pathway. In addition, NLRX1 also induces cell death by inhibiting the PI3K-AKT signaling pathway, promoting senescence and reducing invasiveness, which plays a tumor suppressive role.

References:

Singh K., &Singh R.. (2019) NLRX1 regulates TNF-α-induced mitochondria-lysosomal crosstalk to maintain the invasive and metastatic potential of breast cancer cells. Biochim Biophys Acta Mol Basis Dis. 1865(6):1460-1476.
Lei, A. , & Maloy, K. J. . (2016). Colon cancer in the land of nod: nlrx1 as an intrinsic tumor suppressor. Trends in Immunology, 37(9), 569-570.
Kors, L. , Rampanelli, E. , Stokman, G. , Butter, L. , Held, N. M. , & Claessen, N. , et al. (2018). Deletion of nlrx1 increases fatty acid metabolism and prevents diet-induced hepatic steatosis and metabolic syndrome. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, S0925443918300838.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry