Ubiquinol-cytochrome c reductase binding protein (UQCRB) is one of the subunits of mitochondrial complex III and is a target protein of the natural anti-angiogenic small molecule terpestacin. Previously, the biological role of UQCRB was thought to be limited to the maintenance of complex III. However, the identification and validation of UQCRB as a target protein of terpestacin enabled the role of UQCRB in oxygen sensing and angiogenesis to be elucidated. To explore the biological role of this protein further, UQCRB mutant stable cell lines were generated on the basis of a human case report. We demonstrated that these cell lines exhibited glycolytic and pro-angiogenic activities via mitochondrial reactive oxygen species (mROS)-mediated HIF1 signal transduction. Furthermore, a morphological abnormality in mitochondria was detected in UQCRB mutant stable cell lines. In addition, the proliferative effect of the UQCRB mutants was significantly regulated by the UQCRB inhibitors terpestacin and A1938. Collectively, these results provide a molecular basis for UQCRB-related biological processes and reveal potential key roles of UQCRB in angiogenesis and mitochondria-mediated metabolic disorders.
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2014 Dec 12|
Bibliographical noteFunding Information:
This study was partly supported by Grants from the National Research Foundation of Korea funded by the Korean Government ( 2010-0017984 , 2012M3A9D1054520 ), the Translational Research Center for Protein Function Control, KRF ( 2009-0083522 ), the Next-Generation BioGreen 21 Program (No. PJ0079772012), Rural Development Administration, National R&D Program, Ministry of Health &Welfare (0620360-1), and the Brain Korea 21 Plus Project, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology