UQCRB regulates mitochondrial energy metabolism by promoting COX5 A in atherosclerotic endothelial dysfunction.

Mitochondrial dysfunction plays a critical role in the onset and progression of Atherosclerosis (AS). The ubiquinol-cytochrome c reductase binding protein (UQCRB) is an essential subunit of the mitochondrial respiratory chain. The objective of this study was to investigate whether UQCRB improves endothelial dysfunction in AS by upregulating cytochrome c oxidase subunit 5A (COX5A), thereby regulating mitochondrial energy metabolism, reducing inflammation, and preventing apoptosis. To explore the biological role of UQCRB in AS, we found that UQCRB was significantly downregulated in AS, based on bioinformatics analysis and clinical patient data. In vitro, overexpression of UQCRB significantly increased COX5A protein expression in response to oxidized low-density lipoprotein (OX-LDL), enhanced mitochondrial membrane potential, boosted ATP production, and reduced reactive oxygen species (ROS) levels. Furthermore, the secretion of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, was decreased, and the apoptosis rate was significantly reduced. Additionally, the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was lowered, while the level of phosphorylated AMP-activated protein kinase (AMPK) was increased. The small molecule compound Terpestacin targeting UQCRB down-regulated the expression of COX5A in the AS mouse model, exacerbated endothelial dysfunction, and increased inflammation. These findings further corroborated the in vitro results. In conclusion, UQCRB enhances mitochondrial energy metabolism and activates the AMPK pathway while reducing inflammation and apoptosis through the upregulation of COX5A. This study identifies UQCRB as a novel therapeutic target and provides a theoretical foundation for the development of strategies to prevent and treat atherosclerosis.