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A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.cmet.2019.11.020 Hee Chan Yoo 1 , Seung Joon Park 2 , Miso Nam 3 , Juwon Kang 1 , Kibum Kim 2 , Joo Hye Yeo 1 , Joon-Ki Kim 4 , Yunkyung Heo 1 , Hee Seung Lee 5 , Myeong Youl Lee 6 , Chang Woo Lee 6 , Jong Soon Kang 6 , Yun-Hee Kim 4 , Jinu Lee 1 , Junjeong Choi 1 , Geum-Sook Hwang 3 , Seungmin Bang 5 , Jung Min Han 2
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-13 , DOI: 10.1016/j.cmet.2019.11.020 Hee Chan Yoo 1 , Seung Joon Park 2 , Miso Nam 3 , Juwon Kang 1 , Kibum Kim 2 , Joo Hye Yeo 1 , Joon-Ki Kim 4 , Yunkyung Heo 1 , Hee Seung Lee 5 , Myeong Youl Lee 6 , Chang Woo Lee 6 , Jong Soon Kang 6 , Yun-Hee Kim 4 , Jinu Lee 1 , Junjeong Choi 1 , Geum-Sook Hwang 3 , Seungmin Bang 5 , Jung Min Han 2
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Glutamine is an essential nutrient that regulates energy production, redox homeostasis, and signaling in cancer cells. Despite the importance of glutamine in mitochondrial metabolism, the mitochondrial glutamine transporter has long been unknown. Here, we show that the SLC1A5 variant plays a critical role in cancer metabolic reprogramming by transporting glutamine into mitochondria. The SLC1A5 variant has an N-terminal targeting signal for mitochondrial localization. Hypoxia-induced gene expression of the SLC1A5 variant is mediated by HIF-2α. Overexpression of the SLC1A5 variant mediates glutamine-induced ATP production and glutathione synthesis and confers gemcitabine resistance to pancreatic cancer cells. SLC1A5 variant knockdown and overexpression alter cancer cell and tumor growth, supporting an oncogenic role. This work demonstrates that the SLC1A5 variant is a mitochondrial glutamine transporter for cancer metabolic reprogramming.
中文翻译：
SLC1A5的一个变体是用于癌细胞中代谢重编程的线粒体谷氨酰胺转运蛋白。
谷氨酰胺是调节癌细胞中能量产生，氧化还原稳态和信号传导的必需营养素。尽管谷氨酰胺在线粒体代谢中很重要，但线粒体谷氨酰胺转运蛋白早已为人们所知。在这里，我们显示SLC1A5变体通过将谷氨酰胺转运到线粒体中在癌症代谢重编程中发挥关键作用。SLC1A5变体具有用于线粒体定位的N端靶向信号。缺氧诱导的SLC1A5变体的基因表达是由HIF-2α介导的。SLC1A5变体的过表达介导谷氨酰胺诱导的ATP产生和谷胱甘肽合成，并赋予吉西他滨对胰腺癌细胞的抗性。SLC1A5变体的敲低和过表达改变癌细胞和肿瘤的生长，支持致癌作用。
更新日期：2019-12-19
中文翻译：
SLC1A5的一个变体是用于癌细胞中代谢重编程的线粒体谷氨酰胺转运蛋白。
谷氨酰胺是调节癌细胞中能量产生，氧化还原稳态和信号传导的必需营养素。尽管谷氨酰胺在线粒体代谢中很重要，但线粒体谷氨酰胺转运蛋白早已为人们所知。在这里，我们显示SLC1A5变体通过将谷氨酰胺转运到线粒体中在癌症代谢重编程中发挥关键作用。SLC1A5变体具有用于线粒体定位的N端靶向信号。缺氧诱导的SLC1A5变体的基因表达是由HIF-2α介导的。SLC1A5变体的过表达介导谷氨酰胺诱导的ATP产生和谷胱甘肽合成，并赋予吉西他滨对胰腺癌细胞的抗性。SLC1A5变体的敲低和过表达改变癌细胞和肿瘤的生长，支持致癌作用。
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