Emerging Roles for the Lysosome in Lipid Metabolism.

Emerging Roles for the Lysosome in Lipid Metabolism.
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DOI:
10.1016/j.tcb.2017.07.006
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发表时间:
2017-11
影响因子:
19
通讯作者:
Zoncu R
Zoncu R
中科院分区:
生物学1区
文献类型:
--
作者:
Thelen AM;Zoncu R

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脂质生物合成、运输和储存的精确调节是细胞和生物体内平衡的关键。细胞依赖于复杂但知之甚少的囊泡和非囊泡转运机制网络,以确保脂质有效递送至靶细胞器。溶酶体由于其处理和分选外源性和内源性脂质的能力而处于该网络的十字路口。溶酶体的脂质分选功能与其最近发现的作为代谢指挥和控制中心的作用密切相关,该中心将多种营养线索传递给主生长调节剂,雷帕霉素复合物1(mTORC 1)激酶的机械靶标。反过来,mTORC1有效地驱动合成代谢过程,包括从头脂质合成,同时抑制脂质catalysts。在这里,我们描述了溶酶体在脂质转运和生物合成中的双重作用,并讨论了这两个过程的整合如何在正常生理和疾病中发挥重要作用。
Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and non-vesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic Target of Rapamycin Complex 1 (mTORC1) kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease.
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