Mitochondrially localized EGFR is subjected to autophagic regulation and implicated in cell survival
Mitochondrially localized EGFR is subjected to autophagic regulation and implicated in cell survival
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线粒体定位的 EGFR 受到自噬调节并与细胞存活有关
DOI：
10.4161/auto.5971
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发表时间：
2008-04
期刊：
影响因子：
13.3
通讯作者：
Xi, Zhijun
中科院分区：
文献类型：
--
作者：
Yue, Xiaojing;Song, Weidong;Xin, Zhongcheng;Chen, Liang;Zhang, Wei;Jiang, Xuejun;Xi, Zhijun
虽然表皮生长因子 (EGF) 受体通常被认为是质膜蛋白，但它已在细胞核和亚细胞细胞器中发现。最近，EGF受体（EGFR）的线粒体定位被报道；然而，EGFR 定位于线粒体的分子机制在很大程度上尚不清楚。使用免疫荧光和免疫电子显微镜，我们观察到 EGFR 确实定位于线粒体内。此外，A431 细胞中雷帕霉素处理可增加 EGFR 线粒体易位，而自噬抑制剂 3-甲基腺嘌呤 (3-MA) 的存在可大大减少 EGFR 线粒体易位。小干扰 RNA (siRNA) 进一步证实了通过自噬抑制来减少线粒体 EGFR，从而耗尽必需蛋白 Beclin 1。敲除 Beclin 1 显着减少雷帕霉素诱导的 EGFR 线粒体易位。我们还注意到，当细胞暴露于凋亡诱导剂依托泊苷时，线粒体 EGFR 转移的含量会降低。此外，EGF 治疗或 siRNA 敲低 EGFR 都会导致拥有更多线粒体 EGFR 的细胞的细胞活力大幅下降。综上所述，我们得出结论，EGFR 线粒体定位受自噬或程序性细胞死亡调节，并且与细胞存活相关。
Although generally acknowledged as a plasma membrane protein, the epidermal growth factor (EGF) receptor has been found in the nucleus and subcellular organelles. Recently, the mitochondrial localization of the EGF receptor (EGFR) was reported; nevertheless, the molecular mechanism underlying EGFR localization in mitochondria is largely unknown. Using immunofluorescence and immunoelectron microscopy, we observed that EGFR did localize within mitochondria. Moreover, EGFR mitochondrial translocation can be increased by rapamycin treatment in A431 cells and greatly reduced by the presence of 3-methyladenine (3-MA), an inhibitor of autophagy. The reduction of mitochondrial EGFR via autophagy inhibition is further confirmed by small interference RNA (siRNA), through which the essential protein Beclin 1 was depleted. Knocking down Beclin 1 markedly decreased the mitochondrial translocation of EGFR that was induced by rapamycin. We also noticed that the content of mitochondrial EGFR transfer is decreased when the cells are exposed to the apoptotic inducer etoposide. Additionally, either EGF treatment or EGFR knockdown by siRNA results in a greater decline of cell viability in cells possessing more mitochondrial EGFRs. Taken together, we conclude that EGFR mitochondrial localization is regulated by either autophagy or programmed cell death and is correlated with cell survival.
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影响因子：
3.7
作者：
F. Ballard
通讯作者：
F. Ballard
DOI：
10.1083/jcb.119.2.349
发表时间：
1992-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
den Hartigh JC;van Bergen en Henegouwen PM;Verkleij AJ;Boonstra J
通讯作者：
Boonstra J
影响因子：
21.3
作者：
Lin, SY;Makino, K;Hung, MC
通讯作者：
Hung, MC
影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
DOI：
10.1016/j.bbamcr.2006.07.015
发表时间：
2006-10-01
影响因子：
5.1
作者：
Wolfman, Janice C.;Planchon, Sarah M.;Wolfman, Alan
通讯作者：
Wolfman, Alan