Mitochondrially localized EGFR is independent of its endocytosis and associates with cell viability

• Published in: Acta biochimica et biophysica Sinica 2010-11, Vol.42 (11), p.763-770
• Main Authors: Yao, Yuan, Wang, Gang, Li, Zhe, Yan, Bing, Guo, Yinglu, Jiang, Xuejun, Xi, Zhijun
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; Endocytosis; Epidermal Growth Factor - pharmacology; Etoposide - pharmacology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Immunoblotting; Microscopy, Immunoelectron; Mitochondria - metabolism; Mitochondria - ultrastructure; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mitochondrial Proteins - ultrastructure; Mutation; Protein Transport - drug effects; Quinazolines - pharmacology; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, Epidermal Growth Factor - ultrastructure; 内吞作用; 本地化; 程序性细胞死亡; 线粒体膜; 细胞器; 编程性细胞死亡; 表皮生长因子受体
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmq090

The molecular mechanism factor receptor （EGFR） underlying epidermal growth localization in mitochondria remains largely unknown. Using immune electron microscopy, we validated that EGFR could be localized on either the outer or the inner membrane of mitochondria. Mutant receptor lacked amino acids 646-660 was flawed in migration onto the organelles, whereas the mutated receptor with a defective endocytosis showed a greater capability of moving onto mitochondria upon stimulation of epidermal growth factor （EGF）. Gefltinib, an inhibitor of EGFR kinase, inhibited the receptor endocytosis after short time of treatment, yet, only reduced cell viability as well as the amount of mitochondrial EGFR after longer time of exposure. Moreover, the content of mitochondrial EGFR transfer was decreased when the cells were exposed to the apoptotic inducer etoposide. EGF-induced pro- grammed cell death usually coincided with a decline in mitochondrial EGFR. These data indicated that the mitochondrial-localized EGFR is independent of its internalization and may be correlated with cell survival and participate in the ligand-induced programmed cell death .