Mitochondrially localized EGFR is independent of its endocytosis and associates with cell viability
Mitochondrially localized EGFR is independent of its endocytosis and associates with cell viability
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线粒体定位的 EGFR 独立于其内吞作用并与细胞活力相关
DOI：
10.1093/abbs/gmq090
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发表时间：
2010-11-01
影响因子：
3.7
通讯作者：
Xi, Zhijun
中科院分区：
文献类型：
--
作者：
Yao, Yuan;Wang, Gang;Xi, Zhijun
表皮生长因子受体（EGFR）在线粒体中定位的分子机制仍不清楚。利用免疫电镜，我们证实EGFR可以定位于线粒体的外膜或内膜。缺乏氨基酸646-660的突变受体在迁移到细胞器中是有缺陷的，而具有缺陷的内吞作用的突变受体在表皮生长因子（EGF）的刺激下显示出更大的迁移到线粒体上的能力。EGFR激酶抑制剂吉非替尼在短时间处理后抑制受体内吞，但在较长时间暴露后仅降低细胞活力以及线粒体EGFR的量。凋亡诱导剂足叶乙甙作用后，线粒体EGFR转运蛋白含量降低。EGF诱导的程序性细胞死亡通常与线粒体EGFR的下降相一致。这些数据表明，EGFR的细胞定位是独立的内化，并可能与细胞的生存和参与配体诱导的程序性细胞死亡。
The molecular mechanism underlying epidermal growth factor receptor (EGFR) 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). Gefitinib, 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 programmed 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.