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.

雷帕霉素的 Ser/Thr 激酶机制靶点 (mTOR) 是细胞代谢的中心调节因子。作为 mTOR 复合物 1 (mTORC1) 的一部分，mTOR 整合营养物质、生长因子、能源和氧气水平等信号，并触发促进合成代谢或抑制分解代谢的反应。 mTORC1 信号传导对关键组织和器官的生长和稳态具有广泛的影响，其失调的活性会促进癌症、2 型糖尿病、神经退行性疾病和其他与年龄相关的疾病。 mTORC1 如何整合众多上游线索并将其转化为特定的下游反应是一个悬而未决的问题，对我们理解生理学和疾病机制具有重大影响。在这篇综述中，我们讨论了最近对 mTORC1 及其溶酶体伙伴分子结构的结构和功能见解，这极大地增加了我们对营养依赖性 mTORC1 调节的机制的理解。我们还讨论了异常营养素 mTORC1 信号在多种疾病中的新出现。