Uncovering the biological function of UQCRB, a terpestacin‐binding mitochondrial protein, implies its pro‐angiogenic activity in vitro and in vivo

Abstract

Recently, we identified ubiquinol‐cytochrome c reductase binding protein (UQCRB), one of subunits of mitochondrial Complex III, as a target protein of the anti‐angiogenic natural small molecule, terpestacin. The Complex III of mitochondrial respiratory chain has been considered as a key regulator in hypoxia‐induced angiogenesis through mitochondria‐derived reactive oxygen species (ROS) involved in O2 sensing. Here, cell permeable UQCRB protein is generated using protein transduction domain (PTD), a small peptide transferring its binding complex into the cell, to reveal the biological function of UQCRB. Consequently, intracellular delivery of PTD‐UQCRB fusion protein enhances generation of mitochondrial ROS and HIF‐1α stability. Also, PTD‐UQCRB transduction induces vascular endothelial growth factor (VEGF) expression and invasion of human umbilical vascular endothelial cells (HUVECs) in vitro. Furthermore, trans‐membrane delivery of PTD‐UQCRB enhances wound healing in vivo. These results provide new insights into the function of PTD‐UQCRB in angiogenesis via mitochondria mediated ROS generation and also open new basis on application of PTD‐UQCRB as a pro‐angiogenic agent via regulating mitochondrial function. This study is supported by self‐research funding.