Cells metabolize nutrients for biosynthetic and bioenergetic needs to fuel growth and proliferation. The uptake of nutrients from the environment and their intracellular metabolism is a highly controlled process that involves crosstalk between growth signaling and metabolic pathways. Despite constant fluctuations in nutrient availability and environmental signals, normal cells restore metabolic homeostasis to maintain cellular functions and prevent disease. A central signaling molecule that integrates growth with metabolism is the mechanistic target of rapamycin (mTOR). mTOR is a protein kinase that responds to levels of nutrients and growth signals. mTOR forms two protein complexes, mTORC1, which is sensitive to rapamycin and mTORC2, which is not directly inhibited by this drug. Rapamycin has facilitated the discovery of the various functions of mTORC1 in metabolism. Genetic models that disrupt either mTORC1 or mTORC2 have expanded our knowledge on their cellular, tissue as well as systemic functions in metabolism. Nevertheless, our knowledge on the regulation and functions of mTORC2, particularly in metabolism, has lagged behind. Since mTOR is an important target for cancer, aging and other metabolism-related pathologies, understanding the distinct and overlapping regulation and functions of the two mTOR complexes is vital for the development of more effective therapeutic strategies. This review will discuss the key discoveries and recent findings on the regulation and metabolic functions of the mTOR complexes. We highlight findings from cancer models, but also discuss other examples of the mTOR-mediated metabolic reprogramming occurring in stem and immune cells, type 2 diabetes/obesity, neurodegenerative disorders and aging.

中文翻译：

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mTORC1和mTORC2的调控和代谢功能

细胞代谢营养物质以满足生物合成和生物能量需求，从而促进生长和增殖。从环境中摄取营养物质及其细胞内代谢是一个高度受控的过程，涉及生长信号和代谢途径之间的串扰。尽管营养供应和环境信号不断波动，但正常细胞会恢复代谢稳态以维持细胞功能并预防疾病。将生长与代谢相结合的中心信号分子是雷帕霉素 (mTOR) 的机制靶点。mTOR 是一种蛋白激酶，可对营养水平和生长信号作出反应。mTOR 形成两种蛋白质复合物，mTORC1，对雷帕霉素敏感，mTORC2，不直接被这种药物抑制。雷帕霉素促进了 mTORC1 在代谢中各种功能的发现。破坏 mTORC1 或 mTORC2 的遗传模型扩展了我们对其细胞、组织以及代谢中的系统功能的了解。然而，我们对 mTORC2 的调节和功能的了解，特别是在新陈代谢方面，已经落后了。由于 mTOR 是癌症、衰老和其他代谢相关病理的重要靶标，因此了解两种 mTOR 复合物的独特和重叠调节和功能对于开发更有效的治疗策略至关重要。本综述将讨论关于 mTOR 复合物的调节和代谢功能的主要发现和最新发现。我们强调癌症模型的发现，