Ucp3, or uncoupling protein-3, is a mitochondria-regulatory protein belonging to the mitochondrial uncoupling protein family [2]. It is involved in energy metabolism pathways, with potential functions in maintaining energy homeostasis [1]. Ucp3 may play a role in tuning substrate utilization, favoring lipid oxidation, especially when fat is abundant [1]. It also potentially promotes glucose uptake and oxidation under certain conditions [1].

Findings from Ucp3-knockout (KO) mouse models have provided insights into its functions. Ucp3-KO mice show increased infarct size after cardiac ischemia-reperfusion, accompanied by higher levels of creatine kinase and more pronounced mitochondrial structural changes, indicating that Ucp3 deficiency promotes enhanced superoxide generation and mitochondrial structural changes, increasing myocardial vulnerability to injury [4]. In the context of angiotensin II-induced hypertension, Ucp3 haploinsufficiency (ucp3+/-) in rats exacerbates left ventricular diastolic dysfunction, accelerating left ventricular concentric remodeling, interstitial matrix remodeling, and fetal gene reprogramming, while also increasing oxidative stress and impairing protein kinase G signaling [3].

In conclusion, Ucp3 is crucial for energy metabolism, especially in substrate utilization and mitochondrial function. The study of Ucp3 KO mouse models has revealed its significance in diseases related to the heart, such as cardiac ischemia-reperfusion injury and left ventricular diastolic dysfunction during hypertension. These findings help in understanding the biological functions of Ucp3 and may provide potential therapeutic targets for related diseases.

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. Chen, Xu, Ashraf, Sadia, Ashraf, Nadia, Harmancey, Romain. 2021. UCP3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin II-Induced Hypertension. In Journal of the American Heart Association, 10, e022556. doi:10.1161/JAHA.121.022556. https://pubmed.ncbi.nlm.nih.gov/34533037/

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/