氨基酸的双向运输调节mTOR和自噬

Bidirectional transport of amino acids regulates mTOR and autophagy.

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|核心内容：

氨基酸是激活哺乳动物靶标雷帕霉素(MTOR)激酶所必需的，它调节蛋白质翻译、细胞生长和自噬。

允许氨基酸进入细胞并向mTOR传递信号的细胞表面转运体是未知的。

我们发现细胞摄取L-谷氨酰胺及其随后在必需氨基酸(EAA)存在下的快速外流是激活mTOR的限速步骤。

L-谷氨酰胺摄取受SLC1A5调节，SLC1A5功能丧失会抑制细胞生长并激活自噬。

L-谷氨酰胺敏感性的分子基础是SLC7A5/SLC3A2，它是一种双向转运蛋白，调节着L-谷氨酰胺同时流出细胞和L-亮氨酸/EAA向细胞内的转运。

某些基础细胞水平较高的L-谷氨酰胺的肿瘤细胞系可绕过摄取L-谷氨酰胺的需要，并为mTOR激活做好准备。

因此，L-谷氨酰胺通量调节mTOR、翻译和自噬，以协调细胞的生长和增殖。

原文摘要：

Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. 

Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. 

L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. 

The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. 

Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. 

Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.

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参考文献：https://sci-hub.se/10.1016/j.cell.2008.11.044

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