Every cell must satisfy basic requirements for nutrient sensing, utilization and recycling through macromolecular breakdown to coordinate programmes for growth, repair and stress adaptation. The lysosome orchestrates these key functions through the synchronised interplay between hydrolytic enzymes, nutrient transporters and signalling factors, which together enable metabolic coordination with other organelles and regulation of specific gene expression programmes. In this Review, we discuss recent findings on lysosome-dependent signalling pathways, focusing on how the lysosome senses nutrient availability through its physical and functional association with mechanistic target of rapamycin complex 1 (mTORC1) and how, in response, the microphthalmia/transcription factor E (MiT/TFE) transcription factors exert feedback regulation on lysosome biogenesis. We also highlight the emerging interactions of lysosomes with other organelles, which contribute to cellular homeostasis. Lastly, we discuss how lysosome dysfunction contributes to diverse disease pathologies and how inherited mutations that compromise lysosomal hydrolysis, transport or signalling components lead to multi-organ disorders with severe metabolic and neurological impact. A deeper comprehension of lysosomal composition and function, at both the cellular and organismal level, may uncover fundamental insights into human physiology and disease.

每个细胞都必须通过大分子分解来满足营养感应、利用和回收的基本要求，以协调生长、修复和应激适应程序。溶酶体通过水解酶、营养转运蛋白和信号因子之间的同步相互作用来协调这些关键功能，它们共同实现与其他细胞器的代谢协调和特定基因表达程序的调节。在这篇综述中，我们讨论了关于溶酶体依赖性信号通路的最新发现，重点关注溶酶体如何通过其与雷帕霉素复合物 1 (mTORC1) 机制靶点的物理和功能关联来感知营养物质的可用性，以及小眼/转录因子如何响应E (MiT/TFE) 转录因子对溶酶体生物发生发挥反馈调节作用。我们还强调了溶酶体与其他细胞器的新兴相互作用，这有助于细胞稳态。最后，我们讨论了溶酶体功能障碍如何导致多种疾病病理，以及损害溶酶体水解、运输或信号成分的遗传突变如何导致多器官疾病，并产生严重的代谢和神经系统影响。在细胞和有机体水平上更深入地理解溶酶体的组成和功能，可能会揭示对人类生理学和疾病的基本见解。