Ucp2, an uncoupling protein homolog to UCP1, is a mitochondrial anion carrier protein located in the mitochondrial inner membrane [2,3,4]. It uncouples oxidative phosphorylation from ATP production by dissipating the proton gradient across the inner mitochondrial membrane, regulating mitochondrial ATP production and the generation of reactive oxygen species (ROS) [2,4]. Ucp2 is involved in multiple pathways such as fatty acid metabolism, mitochondrial calcium uptake, and is related to processes like energy expenditure, insulin secretion, and cell proliferation and death [3]. Its role in maintaining cellular homeostasis makes it biologically important, and genetic models like KO/CKO mouse models are valuable for studying its functions [5].

In endothelial cells, EC-specific Ucp2 knockout mice studies showed that Ucp2 is a mechanosensitive gene under the control of fluid shear stress and KLF2. Ucp2 deficiency promotes atherogenesis, collagen production, and atherosclerotic plaque formation, indicating its role in suppressing atherosclerosis [1]. In podocytes, podocyte-specific Ucp2-KO mice demonstrated that Ucp2 protects against hyperglycemia-induced podocyte injury by promoting autophagy, and its deficiency impairs autophagy and exacerbates podocyte injury and proteinuria in diabetic nephropathy [5].

In conclusion, Ucp2 plays essential roles in various biological processes such as regulating oxidative stress, cellular metabolism, and autophagy. Through KO/CKO mouse models, its significance in diseases like atherosclerosis and diabetic nephropathy has been revealed. These models help understand the mechanisms by which Ucp2 functions, providing potential therapeutic directions for related diseases.

References:

1. Luo, Jiang-Yun, Cheng, Chak Kwong, He, Lei, Jo, Hanjoong, Huang, Yu. 2022. Endothelial UCP2 Is a Mechanosensitive Suppressor of Atherosclerosis. In Circulation research, 131, 424-441. doi:10.1161/CIRCRESAHA.122.321187. https://pubmed.ncbi.nlm.nih.gov/35899624/

2. Nesci, Salvatore, Rubattu, Speranza. 2024. UCP2, a Member of the Mitochondrial Uncoupling Proteins: An Overview from Physiological to Pathological Roles. In Biomedicines, 12, . doi:10.3390/biomedicines12061307. https://pubmed.ncbi.nlm.nih.gov/38927514/

3. Li, Jinran, Jiang, Rihua, Cong, Xianling, Zhao, Yunfeng. 2019. UCP2 gene polymorphisms in obesity and diabetes, and the role of UCP2 in cancer. In FEBS letters, 593, 2525-2534. doi:10.1002/1873-3468.13546. https://pubmed.ncbi.nlm.nih.gov/31330574/

4. Toda, Chitoku, Diano, Sabrina. 2014. Mitochondrial UCP2 in the central regulation of metabolism. In Best practice & research. Clinical endocrinology & metabolism, 28, 757-64. doi:10.1016/j.beem.2014.02.006. https://pubmed.ncbi.nlm.nih.gov/25256770/

5. Yang, Qianqian, Yang, Shuqing, Liang, Yuehong, Wen, Ping, Yang, Junwei. 2023. UCP2 deficiency impairs podocyte autophagy in diabetic nephropathy. In Biochimica et biophysica acta. Molecular basis of disease, 1869, 166705. doi:10.1016/j.bbadis.2023.166705. https://pubmed.ncbi.nlm.nih.gov/37023910/