Carroll Bernadette, Dunlop Elaine A
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, U.K.
Division of Cancer and Genetics, Cardiff University, Cardiff, U.K.
Biochem J. 2017 Apr 13;474(9):1453-1466. doi: 10.1042/BCJ20160780.
Much attention has recently been focussed on the lysosome as a signalling hub. Following the initial discovery that localisation of the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), to the lysosome was essential for mTORC1 activation, the field has rapidly expanded to reveal the role of the lysosome as a platform permitting the co-ordination of several homeostatic signalling pathways. Much is now understood about how the lysosome contributes to amino acid sensing by mTORC1, the involvement of the energy-sensing kinase, AMP-activated protein kinase (AMPK), at the lysosome and how both AMPK and mTORC1 signalling pathways feedback to lysosomal biogenesis and regeneration following autophagy. This review will cover the classical role of the lysosome in autophagy, the dynamic signalling interactions which take place on the lysosomal surface and the multiple levels of cross-talk which exist between lysosomes, AMPK and mTORC1.
最近,溶酶体作为一个信号枢纽受到了广泛关注。在最初发现营养敏感激酶——雷帕霉素复合物1的哺乳动物靶点(mTORC1)定位于溶酶体对mTORC1激活至关重要之后,该领域迅速扩展,揭示了溶酶体作为一个平台允许协调几种稳态信号通路的作用。现在,关于溶酶体如何促进mTORC1对氨基酸的感知、能量感应激酶——AMP激活的蛋白激酶(AMPK)在溶酶体中的参与,以及AMPK和mTORC1信号通路如何在自噬后反馈到溶酶体生物发生和再生,人们已经有了很多了解。本综述将涵盖溶酶体在自噬中的经典作用、在溶酶体表面发生的动态信号相互作用,以及溶酶体、AMPK和mTORC1之间存在的多层次相互作用。