Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Int J Mol Sci. 2018 Mar 12;19(3):818. doi: 10.3390/ijms19030818.
The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cellular growth and metabolism with environmental inputs to ensure that cells grow only under favourable conditions. When active, mTORC1 stimulates biosynthetic pathways including protein, lipid and nucleotide synthesis and inhibits cellular catabolism through repression of the autophagic pathway, thereby promoting cell growth and proliferation. The recruitment of mTORC1 to the lysosomal surface has been shown to be essential for its activation. This finding has significantly enhanced our knowledge of mTORC1 regulation and has focused the attention of the field on the lysosome as a signalling hub which coordinates several homeostatic pathways. The intriguing localisation of mTORC1 to the cellular organelle that plays a crucial role in catabolism enables mTORC1 to feedback to autophagy and lysosomal biogenesis, thus leading mTORC1 to enact precise spatial and temporal control of cell growth. This review will cover the signalling interactions which take place on the surface of lysosomes and the cross-talk which exists between mTORC1 activity and lysosomal function.
雷帕霉素靶蛋白复合物 1(mTORC1)将细胞生长和代谢与环境输入联系起来,以确保细胞仅在有利条件下生长。当活跃时,mTORC1 通过抑制自噬途径来刺激包括蛋白质、脂质和核苷酸合成在内的生物合成途径,并抑制细胞分解代谢,从而促进细胞生长和增殖。已经证明,mTORC1 募集到溶酶体表面对于其激活是必不可少的。这一发现极大地提高了我们对 mTORC1 调节的认识,并使该领域将注意力集中在溶酶体作为一个信号枢纽,协调几个体内平衡途径。mTORC1 定位于在分解代谢中起着关键作用的细胞细胞器,这使得 mTORC1 能够反馈到自噬和溶酶体发生,从而使 mTORC1 能够对细胞生长进行精确的时空控制。这篇综述将涵盖发生在溶酶体表面的信号相互作用以及 mTORC1 活性和溶酶体功能之间存在的串扰。