NLRX1, also known as NLR family member X1, is a member of the Nod-like receptor (NLR) family. It localizes to the mitochondrial matrix in resting conditions and has been proposed to regulate multiple cellular processes, including antiviral immunity, apoptosis, ROS generation, mitochondrial metabolism, and mitophagy [2]. It is involved in various signaling pathways such as negatively regulating type-I interferon, attenuating pro-inflammatory NF-κB signaling, and modulating autophagy [3].

In studies related to intervertebral disc degeneration (IDD), the loss of NLRX1 was correlated with nucleus pulposus (NP) cell senescence and IDD progression, involving disordered mitochondrial quality. NLRX1-defective NP cells showed mitochondrial collapse, excessive mitophagy, and aggressive NP cell senescence [1]. In macrophages, NLRX1 knockout (KO) mice had enhanced M2 macrophage polarization and excessive renal fibrosis in chronic obstructive nephropathy, indicating NLRX1's role in preventing such pathological changes [4].

In conclusion, NLRX1 plays essential biological functions in regulating mitochondrial dynamics, mitophagy, immune responses, and cell metabolism. Studies using NLRX1 KO mouse models have revealed its significance in diseases like IDD and chronic obstructive nephropathy, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Song, Yu, Liang, Huaizhen, Li, Gaocai, Wang, Kun, Yang, Cao. 2023. The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn2+ trafficking. In Autophagy, 20, 809-829. doi:10.1080/15548627.2023.2274205. https://pubmed.ncbi.nlm.nih.gov/37876250/

2. Bi, Paul Y, Killackey, Samuel A, Schweizer, Linus, Girardin, Stephen E. 2023. NLRX1: Versatile functions of a mitochondrial NLR protein that controls mitophagy. In Biomedical journal, 47, 100635. doi:10.1016/j.bj.2023.100635. https://pubmed.ncbi.nlm.nih.gov/37574163/

3. Nagai-Singer, Margaret A, Morrison, Holly A, Allen, Irving C. 2019. NLRX1 Is a Multifaceted and Enigmatic Regulator of Immune System Function. In Frontiers in immunology, 10, 2419. doi:10.3389/fimmu.2019.02419. https://pubmed.ncbi.nlm.nih.gov/31681307/

4. Liu, Ye, Kors, Lotte, Butter, Loes M, Florquin, Sandrine, Tammaro, Alessandra. 2023. NLRX1 Prevents M2 Macrophage Polarization and Excessive Renal Fibrosis in Chronic Obstructive Nephropathy. In Cells, 13, . doi:10.3390/cells13010023. https://pubmed.ncbi.nlm.nih.gov/38201227/