Mrpl2-KO Mouse

Mrpl2, a mitochondrial ribosomal protein gene, is an essential component for the structural and functional integrity of the mitoribosome complex [1]. Mitoribosomes are crucial for mitochondrial protein synthesis, which is involved in energy production through oxidative phosphorylation and other key cellular processes. The lack of functional redundancy among mitochondrial ribosomal protein genes, including Mrpl2, suggests each has a unique and essential role in the mitoribosome [1].

Long-term exposure to third-hand smoke was found to accelerate biological aging. Proteomic analyses identified MRPL2 as a key protein in this process, linking its expression to mitochondrial dysfunction and oxidative stress [2]. In chronic obstructive pulmonary disease (COPD), Mrpl2 was nominated as a causal mitochondria-related differential expression gene, with its predominant expression in pulmonary macrophages [3]. In neuropathic pain-induced depression, Mrpl2 was among the key genes with higher expression, related to mitochondrial translation termination and other functions [4]. In diffuse large B-cell lymphoma, Mrpl2 was one of the 18 prognostic mitochondria-related genes used to construct a risk model [5]. In a study on fluorosis, Mrpl2 was identified as a hub gene among the overlapping genes of differentially expressed genes and cuprotosis-related genes, associated with immune response and inflammation [7]. A reduction-of-function mutant allele in the Caenorhabditis elegans mrpl-2 gene activated the mitochondrial unfolded protein response (UPRmt) in a diet-dependent manner, leading to longer lifespan and better survival during pathogen infection [6]. In an Alzheimer's disease mouse model, the protein expression of Mrpl2 was significantly downregulated in the retinas of older mice, which might be considered a toxicity effect related to altered protein biosynthesis [8].

In conclusion, Mrpl2 is essential for the mitoribosome complex and mitochondrial function. Its dysregulation is associated with multiple disease conditions such as aging, COPD, neuropathic pain-induced depression, lymphoma, fluorosis, and potentially Alzheimer's disease-related retinal pathology. Studies, including those using genetic models like the mutant allele in C. elegans, have provided insights into its role in biological processes and disease mechanisms.

References:

1. Cheong, Agnes, Lingutla, Ranjana, Mager, Jesse. 2020. Expression analysis of mammalian mitochondrial ribosomal protein genes. In Gene expression patterns : GEP, 38, 119147. doi:10.1016/j.gep.2020.119147. https://pubmed.ncbi.nlm.nih.gov/32987154/

2. Jiang, Wenbo, Liu, Xin, Lei, Qianqian, Wu, Huanyu, Sun, Changhao. 2024. Long-term exposure to third-hand smoke could accelerate biological aging via mitochondrial dysfunction: Evidence from population and animal studies. In Journal of hazardous materials, 480, 136061. doi:10.1016/j.jhazmat.2024.136061. https://pubmed.ncbi.nlm.nih.gov/39393317/

3. Zou, Xiaoli, Huang, Qiqing, Kang, Tutu, Cao, Chenxi, Wu, Jianqing. 2025. An integrated investigation of mitochondrial genes in COPD reveals the causal effect of NDUFS2 by regulating pulmonary macrophages. In Biology direct, 20, 4. doi:10.1186/s13062-025-00593-3. https://pubmed.ncbi.nlm.nih.gov/39789601/

4. Li, Ling, Su, Hong, Yang, Yang, Zhang, Xi, Su, Shengyong. . Screening key genes related to neuropathic pain-induced depression through an integrative bioinformatics analysis. In Annals of translational medicine, 10, 1348. doi:10.21037/atm-22-5820. https://pubmed.ncbi.nlm.nih.gov/36660683/

5. Zhou, Zhen-Zhong, Lu, Jia-Chen, Guo, Song-Bin, Zhou, Hui, Huang, Wei-Juan. . A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features. In Cancer medicine, 14, e70602. doi:10.1002/cam4.70602. https://pubmed.ncbi.nlm.nih.gov/39811936/

6. Amin, Mustafi Raisa, Mahmud, Siraje Arif, Dowgielewicz, Jonathan L, Sapkota, Madhab, Pellegrino, Mark W. 2020. A novel gene-diet interaction promotes organismal lifespan and host protection during infection via the mitochondrial UPR. In PLoS genetics, 16, e1009234. doi:10.1371/journal.pgen.1009234. https://pubmed.ncbi.nlm.nih.gov/33338044/

7. Ba, Ruijie, Liu, Bin, Feng, Zichen, Zhou, Guoyu, Ba, Yue. 2025. Comprehensive Analysis of Immune Characteristics of Fluorosis and Cuprotosis-Related Genes in Fluorosis Targeted Drugs. In Biological trace element research, , . doi:10.1007/s12011-025-04517-0. https://pubmed.ncbi.nlm.nih.gov/39836320/

8. Mirzaei, Mehdi, Pushpitha, Kanishka, Deng, Liting, Graham, Stuart L, Gupta, Vivek K. 2019. Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer's Disease. In Molecular neurobiology, 56, 6017-6034. doi:10.1007/s12035-019-1479-4. https://pubmed.ncbi.nlm.nih.gov/30707393/