mTOR（机械靶向雷帕霉素的丝/苏氨酸激酶）是细胞代谢的中央调节因子。作为mTOR复合物1（mTORC1）的一部分，mTOR集成了诸如营养物水平、生长因子、能量来源和氧气水平等信号，并触发相应的反应，从而提高合成代谢或抑制分解代谢。mTORC1信号传导对关键组织和器官的生长和稳态有广泛的影响，其失调的活性促进了癌症、2型糖尿病、神经退行性疾病和其他与年龄相关的疾病。mTORC1如何整合众多的上游信号，并将其转化为特定的下游反应是一个重要的问题，对我们理解生理学和疾病机制具有重要意义。在本综述中，我们讨论了最新的mTORC1分子结构和功能洞见以及其与溶酶体伙伴的关联，这些研究大大增加了我们对营养相关的mTORC1调控的机制理解。我们还讨论了异常营养-mTORC1信号在多种疾病中的新发现。© 2023. Springer Nature Limited.

The Ser/Thr kinase mechanistic target of rapamycin (mTOR) is a central regulator of cellular metabolism. As part of mTOR complex 1 (mTORC1), mTOR integrates signals such as the levels of nutrients, growth factors, energy sources and oxygen, and triggers responses that either boost anabolism or suppress catabolism. mTORC1 signalling has wide-ranging consequences for the growth and homeostasis of key tissues and organs, and its dysregulated activity promotes cancer, type 2 diabetes, neurodegeneration and other age-related disorders. How mTORC1 integrates numerous upstream cues and translates them into specific downstream responses is an outstanding question with major implications for our understanding of physiology and disease mechanisms. In this Review, we discuss recent structural and functional insights into the molecular architecture of mTORC1 and its lysosomal partners, which have greatly increased our mechanistic understanding of nutrient-dependent mTORC1 regulation. We also discuss the emerging involvement of aberrant nutrient-mTORC1 signalling in multiple diseases.© 2023. Springer Nature Limited.