mTORC1 as the main gateway to autophagy.
mTORC1 as the main gateway to autophagy.
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DOI：
10.1042/ebc20170027
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发表时间：
2017-12-12
影响因子：
6.4
通讯作者：
Korolchuk VI
中科院分区：
文献类型：
--
作者：
Rabanal-Ruiz Y;Otten EG;Korolchuk VI
细胞和生物体必须协调其代谢活动与环境的变化，以确保只有在条件有利时才能生长。为了维持细胞内稳态，细胞成分的合成和降解之间的严格调节是必不可少的。在细胞营养感测的中心是雷帕霉素复合物1（mTORC 1）的机制靶标，其将环境线索（包括营养和生长因子可用性以及应激）与代谢过程连接，以保持细胞内稳态。在营养丰富的条件下，mTORC 1通过刺激生物合成途径（包括蛋白质、脂质和核苷酸的合成）以及通过抑制自噬途径抑制细胞增殖来促进细胞生长。它与能量传感器AMP激活的蛋白激酶（AMPK）的密切信号相互作用决定了细胞是否积极支持合成代谢或分解代谢过程。强调mTORC 1在协调细胞代谢中的作用，其失调与从代谢紊乱到许多癌症的许多人类疾病有关。虽然mTORC 1可以通过许多不同的输入来调节，但氨基酸代表了无法通过任何其他刺激来补偿的原始线索。在过去的几年里，对氨基酸如何向mTORC 1发出信号的理解大大增加;然而，这一研究领域仍然是生物医学科学的热门话题。目前的想法和模型提出来解释氨基酸传感，mTORC 1信号和自噬之间的相互关系是本次审查的主题。
Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis. Under nutrient-rich conditions mTORC1 promotes cell growth by stimulating biosynthetic pathways, including synthesis of proteins, lipids and nucleotides, and by inhibiting cellular catabolism through repression of the autophagic pathway. Its close signalling interplay with the energy sensor AMP-activated protein kinase (AMPK) dictates whether the cell actively favours anabolic or catabolic processes. Underlining the role of mTORC1 in the coordination of cellular metabolism, its deregulation is linked to numerous human diseases ranging from metabolic disorders to many cancers. Although mTORC1 can be modulated by a number of different inputs, amino acids represent primordial cues that cannot be compensated for by any other stimuli. The understanding of how amino acids signal to mTORC1 has increased considerably in the last years; however this area of research remains a hot topic in biomedical sciences. The current ideas and models proposed to explain the interrelationship between amino acid sensing, mTORC1 signalling and autophagy is the subject of the present review.