mTORC1-mediated amino acid signaling is critical for cell fate determination under transplant-induced stress
mTORC1-mediated amino acid signaling is critical for cell fate determination under transplant-induced stress
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DOI：
10.1002/1873-3468.14008
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发表时间：
2020-12-08
期刊：
影响因子：
3.5
通讯作者：
Liu, Han
中科院分区：
文献类型：
--
作者：
Cheng, Xiaoyan;Ge, Maolin;Liu, Han
体外操作细胞的移植广泛用于血液学。虽然移植被公认为对移植的细胞施加严重的压力，但移植诱导的压力的性质仍然难以捉摸。在这里，我们提出，缺乏氨基酸在血清中是移植引起的压力的主要原因。从机制上讲，氨基酸缺乏会降低蛋白质合成和营养消耗。然而，在AKT和ERK过度活跃的细胞中，mTORC 1并未受到抑制，蛋白质合成仍然相对较高。这种受损的信号传导导致营养消耗、细胞周期阻滞，并最终导致自噬和细胞死亡，这可以通过放线菌酮或mTORC 1抑制剂来抑制。因此，mTORC1介导的氨基酸信号传导在移植诱导的应激下的细胞命运决定中是至关重要的，并且蛋白质合成抑制可以提高移植效率。
Transplantation of in vitro-manipulated cells is widely used in hematology. While transplantation is well recognized to impose severe stress on transplanted cells, the nature of transplant-induced stress remains elusive. Here, we propose that the lack of amino acids in serum is the major cause of transplant-induced stress. Mechanistically, amino acid deficiency decreases protein synthesis and nutrient consummation. However, in cells with overactive AKT and ERK, mTORC1 is not inhibited and protein synthesis remains relatively high. This impaired signaling causes nutrient depletion, cell cycle block, and eventually autophagy and cell death, which can be inhibited by cycloheximide or mTORC1 inhibitors. Thus, mTORC1-mediated amino acid signaling is critical in cell fate determination under transplant-induced stress, and protein synthesis inhibition can improve transplantation efficiency.