Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening

• Published in: Biochemical and biophysical research communications 2008-08, Vol.373 (1), p.58-63
• Main Authors: Eun, So Young, Woo, Im Sun, Jang, Han-Su, Jin, Hana, Kim, Min Young, Kim, Hye Jung, Lee, Jae Heun, Chang, Ki Churl, Kim, Jin-Hoi, Seo, Han Geuk
• Format: Article
• Language: English
• Subjects: 4-HPR; Antineoplastic Agents - pharmacology; Apoptosis; Bax; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Cell Line, Tumor; COX6A1; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Fenretinide - pharmacology; Gene Library; Humans; JNK; Reactive Oxygen Species - metabolism; ROS; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Two-Hybrid System Techniques
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.05.178

Human cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1) was identified as a novel suppressor of Bcl-2-associated X protein (Bax)-mediated cell death using yeast-based functional screening of a mammalian cDNA library. The overexpression of COX6A1 significantly suppressed Bax- and N-(4-hydroxyphenyl)retinamide (4-HPR)-induced apoptosis in yeast and human glioblastoma-derived U373MG cells, respectively. The generation of reactive oxygen species (ROS) in response to Bax or 4-HPR was inhibited in yeast and U373MG cells that expressed COX6A1, indicating that COX6A1 exerts a protective effect against ROS-induced cell damage. 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3 were markedly attenuated in U373MG cells that stably expressed COX6A1. Our results demonstrate that yeast-based functional screening of human genes for inhibitors of Bax-sensitivity in yeast identified a protein that not only suppresses the toxicity of Bax in yeast, but also has a potential role in protecting mammalian cells from 4-HPR-induced apoptosis.