NDUFA4L2, an important mitochondrial respiratory chain subunit, is involved in cellular energy metabolism. It has been associated with multiple biological processes and diseases. It may play a role in regulating DNA-related functions and immune cell infiltration, and is also linked to pathways like "Metabolic Reprogramming in Cancer" and "Glycolysis Activation in Cancer (Warburg Effect)" [1,2].

In various cancers, NDUFA4L2 shows distinct effects. In colorectal cancer, its high expression is related to poor survival and immune infiltrations, making it a potential prognostic biomarker [1]. In clear cell renal cell carcinoma, it reduces mitochondrial respiration, affects lysosomal trafficking, and may regulate lysosomal functions [2]. In HER2-positive breast cancer, it promotes trastuzumab resistance by enhancing aerobic glycolysis and suppressing ROS production [4]. In glioblastoma, it promotes tumor progression, and apatinib can target it [6]. In colon adenocarcinoma, hypoxia-induced NDUFA4L2 promotes tumor development through the ROS-mediated PI3K/AKT pathway [8]. In osteosarcoma, it promotes metastasis and epithelial-mesenchymal transition by inhibiting ROS production [9]. In smooth muscle, it promotes vascular remodeling in hypoxic pulmonary arterial hypertension [3]. In skeletal muscle, it is a regulator of muscle mass and force, and its induction reduces mitochondrial activity leading to muscle wasting [5]. In non-small cell lung cancer, it promotes cell vitality by repressing oxidative stress [7].

In conclusion, NDUFA4L2 is a crucial factor in cellular energy metabolism and is significantly associated with various diseases, especially cancers. Its role in promoting tumor progression in multiple cancer types, as well as its impact on muscle-related and vascular-related biological processes, highlights its importance. Functional studies of NDUFA4L2 help in understanding disease mechanisms and may provide new therapeutic targets.

References:

1. Lin, Yuning, Xie, Hongyan, Zhao, Wenzhen, Li, Ying, Zhang, Zhongying. . NDUFA4L2 is a novel biomarker for colorectal cancer through bioinformatics analysis. In Medicine, 102, e35893. doi:10.1097/MD.0000000000035893. https://pubmed.ncbi.nlm.nih.gov/37933010/

2. Kubala, Jaclyn M, Laursen, Kristian B, Schreiner, Ryan, Heller, Daniel A, Gudas, Lorraine J. . NDUFA4L2 reduces mitochondrial respiration resulting in defective lysosomal trafficking in clear cell renal cell carcinoma. In Cancer biology & therapy, 24, 2170669. doi:10.1080/15384047.2023.2170669. https://pubmed.ncbi.nlm.nih.gov/36722045/

3. Liu, Yun, Nie, Xiaowei, Zhu, Jinquan, Wang, Qian, Sun, Zengxian. 2020. NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension. In Journal of cellular and molecular medicine, 25, 1221-1237. doi:10.1111/jcmm.16193. https://pubmed.ncbi.nlm.nih.gov/33340241/

4. Yuan, Yuan, Gao, Huanyao, Zhuang, Yongxian, Zhang, Lili, Wang, Liewei. 2021. NDUFA4L2 promotes trastuzumab resistance in HER2-positive breast cancer. In Therapeutic advances in medical oncology, 13, 17588359211027836. doi:10.1177/17588359211027836. https://pubmed.ncbi.nlm.nih.gov/34276814/

5. Liu, Zhengye, Chaillou, Thomas, Santos Alves, Estela, Tavi, Pasi, Lanner, Johanna T. . Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e22010. doi:10.1096/fj.202100066R. https://pubmed.ncbi.nlm.nih.gov/34724256/

6. Chen, Zheng, Wei, Xiangyu, Wang, Xueyi, Li, Shiting, Zheng, Xuesheng. 2021. NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib. In Cell death & disease, 12, 377. doi:10.1038/s41419-021-03646-3. https://pubmed.ncbi.nlm.nih.gov/33828084/

7. Meng, Lifei, Yang, Xuhui, Xie, Xiao, Wang, Mingsong. 2019. Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress. In Thoracic cancer, 10, 676-685. doi:10.1111/1759-7714.12984. https://pubmed.ncbi.nlm.nih.gov/30710412/

8. Ye, Nianyuan, Wang, Yibo, Jiang, Peng, Zhang, Zheng, Xi, Cheng. 2023. Hypoxia-induced the upregulation of NDUFA4L2 promoted colon adenocarcinoma progression through ROS-mediated PI3K/AKT pathway. In Cytotechnology, 75, 461-472. doi:10.1007/s10616-023-00590-2. https://pubmed.ncbi.nlm.nih.gov/37841958/

9. Xu, Wen-Ning, Yang, Run-Ze, Zheng, Huo-Liang, Jiang, Lei-Sheng, Jiang, Sheng-Dan. 2020. NDUFA4L2 Regulated by HIF-1α Promotes Metastasis and Epithelial-Mesenchymal Transition of Osteosarcoma Cells Through Inhibiting ROS Production. In Frontiers in cell and developmental biology, 8, 515051. doi:10.3389/fcell.2020.515051. https://pubmed.ncbi.nlm.nih.gov/33330441/