AMPK: guardian of metabolism and mitochondrial homeostasis.

AMPK: guardian of metabolism and mitochondrial homeostasis.
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AMPK:代谢和线粒体稳态的监护人。

DOI:
10.1038/nrm.2017.95
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发表时间:
2018-03
期刊:
Nature reviews. Molecular cell biology
影响因子:
--
通讯作者:
Shaw RJ
Shaw RJ
中科院分区:
其他
文献类型:
--
作者:
Herzig S;Shaw RJ

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细胞不断地调整它们的新陈代谢以满足它们的能量需求,并对营养物质的可用性做出反应。真核生物已经进化出一个非常复杂的系统,通过丝氨酸/苏氨酸激酶amp激活蛋白激酶(AMPK)复合物来感知低细胞ATP水平。在低能量条件下,AMPK磷酸化特定的酶和生长控制节点,增加ATP的产生,减少ATP的消耗。在过去的十年中,许多新的AMPK底物的发现使得人们对细胞代谢从合成代谢到分解代谢的重新编程所需的最少步骤有了更全面的了解。这种能量开关控制着细胞生长和其他一些细胞过程,包括脂质和葡萄糖代谢以及自噬。最近的研究表明,AMPK的一个古老功能是促进线粒体健康,并且多个新发现的AMPK靶点涉及线粒体稳态的各个方面,包括线粒体自噬。本文讨论了AMPK如何作为细胞对能量应激和线粒体损伤反应的中心介质,并协调自噬和线粒体生物学的多个特征。
Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.
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