Ucp3, or uncoupling protein-3, is a mitochondria-regulatory protein belonging to the mitochondrial uncoupling protein family [2]. It has potential energy-homeostatic functions, with its expression being highest in murine brown adipose tissue, and also present in skeletal muscle and heart [2]. It is thought to be involved in pathways related to energy metabolism, lipid oxidation, and glucose metabolism [1]. Genetic models, such as knockout mice, have been crucial in studying its function.

In Ucp3-knockout (Ucp3-/-) mice, non-polarized, activated T cells (Th0 cells) produced more IL-2, had increased expression of CD25 and CD69, and were more proliferative than those from wild-type mice. This indicated that Ucp3 restricts the activation of naive T cells [3]. Ucp3-/-CD4 + T cells also showed an altered Th17:Treg cell balance, suggesting Ucp3 as a potential target for Th17 cell-mediated autoimmune diseases [3]. In addition, Ucp3-/-mice had larger infarct sizes after cardiac ischemia-reperfusion, along with higher levels of creatine kinase and more pronounced mitochondrial structural changes, showing that Ucp3 deficiency increases myocardial vulnerability to such injury [4].

In conclusion, Ucp3 plays a role in multiple biological processes. Its function in restricting naive T-cell activation and maintaining the Th17:Treg cell balance is significant for autoimmune disease research. Also, its protective role against cardiac ischemia-reperfusion injury is crucial. The study of Ucp3 using knockout mouse models has provided insights into its functions and potential implications in specific disease areas.

References:

1. Della Guardia, Lucio, Luzi, Livio, Codella, Roberto. 2024. Muscle-UCP3 in the regulation of energy metabolism. In Mitochondrion, 76, 101872. doi:10.1016/j.mito.2024.101872. https://pubmed.ncbi.nlm.nih.gov/38499130/

2. Pohl, Elena E, Rupprecht, Anne, Macher, Gabriel, Hilse, Karolina E. 2019. Important Trends in UCP3 Investigation. In Frontiers in physiology, 10, 470. doi:10.3389/fphys.2019.00470. https://pubmed.ncbi.nlm.nih.gov/31133866/

3. O'Connor, Emma B, Muñoz-Wolf, Natalia, Leon, Gemma, Walsh, Patrick T, Porter, Richard K. 2020. UCP3 reciprocally controls CD4+ Th17 and Treg cell differentiation. In PloS one, 15, e0239713. doi:10.1371/journal.pone.0239713. https://pubmed.ncbi.nlm.nih.gov/33211703/

4. Sánchez-Pérez, Patricia, Mata, Ana, Torp, May-Kristin, Stenslokken, Kåre-Olav, Cadenas, Susana. 2023. Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3. In Free radical biology & medicine, 205, 244-261. doi:10.1016/j.freeradbiomed.2023.05.014. https://pubmed.ncbi.nlm.nih.gov/37295539/