The mTOR-Autophagy Axis and the Control of Metabolism.
The mTOR-Autophagy Axis and the Control of Metabolism.
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DOI：
10.3389/fcell.2021.655731
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发表时间：
2021
影响因子：
5.5
通讯作者：
Efeyan A
中科院分区：
文献类型：
--
作者：
Deleyto-Seldas N;Efeyan A
雷帕霉素（mTOR）的机制靶点，细胞代谢的主要调节剂，存在于两种不同的复合物中：mTOR复合物1和mTOR复合物2（mTORC 1和2）。MTORC 1是细胞中大多数能量繁重过程的主开关，在营养充足的情况下驱动细胞生长并构建细胞生物量，相反，在营养限制时允许细胞组分的自噬再循环。mTOR激酶阻断自噬的手段包括直接抑制该过程的早期步骤，以及通过抑制编码结构、调节和催化因子的基因的反式激活来控制细胞的溶酶体降解能力。在抑制mTOR后，细胞组分的自噬再循环导致mTORC 1的再活化;因此，自噬位于mTOR的下游和上游。mTOR通路和自噬之间的功能关系涉及复杂的调节环，其在细胞水平上被显著破译，但在生理水平上不完全理解。然而，来自使用工程小鼠品系的遗传证据提供了重要的见解，即生理性自噬和mTOR活性控制在禁食和营养过载期间发挥的重叠和互补的代谢作用。
The mechanistic target of rapamycin (mTOR), master regulator of cellular metabolism, exists in two distinct complexes: mTOR complex 1 and mTOR complex 2 (mTORC1 and 2). MTORC1 is a master switch for most energetically onerous processes in the cell, driving cell growth and building cellular biomass in instances of nutrient sufficiency, and conversely, allowing autophagic recycling of cellular components upon nutrient limitation. The means by which the mTOR kinase blocks autophagy include direct inhibition of the early steps of the process, and the control of the lysosomal degradative capacity of the cell by inhibiting the transactivation of genes encoding structural, regulatory, and catalytic factors. Upon inhibition of mTOR, autophagic recycling of cellular components results in the reactivation of mTORC1; thus, autophagy lies both downstream and upstream of mTOR. The functional relationship between the mTOR pathway and autophagy involves complex regulatory loops that are significantly deciphered at the cellular level, but incompletely understood at the physiological level. Nevertheless, genetic evidence stemming from the use of engineered strains of mice has provided significant insight into the overlapping and complementary metabolic effects that physiological autophagy and the control of mTOR activity exert during fasting and nutrient overload.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
4.9
作者：
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通讯作者：
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DOI：
10.1126/science.1199498
发表时间：
2011-06-10
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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DOI：
10.1126/science.1259472
发表时间：
2015-01-09
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
11.8
作者：
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通讯作者：
Sabatini, David M.