Homeostatic regulation of energy and metabolic status requires that anabolic and catabolic signaling pathways be precisely regulated and coordinated. Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a mega protein complex that promotes energy-consuming anabolic processes of protein and nucleic acid synthesis as well lipogenesis in times of energy and nutrient abundance. However, it is best characterized as the regulator of steps leading to protein synthesis. The ubiquitin-proteasome proteolytic system (UPS) is a major intracellular proteolytic system whose activity is increased during periods of nutrient scarcity and in muscle wasting conditions such as cachexia. Recent studies have examined the impact of mTORC1 on levels and functions of the 26S proteasome, the mega protease complex of the UPS. Here we first briefly review current understanding of the regulation of mTORC1, the UPS, and the 26S proteasome complex. We then review evidence of the effect of each complex on the abundance and functions of the other. Given the fact that drugs that inhibit either complex are either in clinical trials or are approved for treatment of cancer, a muscle wasting condition, we identify studying the effect of combinatory mTORC1-proteasome inhibition on skeletal muscle mass and health as a critical area requiring investigation.

能量和代谢状态的稳态调节需要精确调节和协调合成代谢和分解代谢信号通路。雷帕霉素复合物 1 (mTORC1) 的哺乳动物/机械靶标是一种巨型蛋白质复合物，可促进蛋白质和核酸合成的耗能合成代谢过程以及能量和营养丰富时的脂肪生成。然而，它的最佳特征是作为导致蛋白质合成的步骤的调节剂。泛素蛋白酶体蛋白水解系统（UPS）是一种主要的细胞内蛋白水解系统，其活性在营养缺乏时期和肌肉萎缩（例如恶病质）期间增加。最近的研究检查了 mTORC1 对 26S 蛋白酶体（UPS 的大型蛋白酶复合物）水平和功能的影响。在这里，我们首先简要回顾一下目前对 mTORC1、UPS 和 26S 蛋白酶体复合物调控的理解。然后，我们审查每种复合物对另一种复合物的丰度和功能影响的证据。鉴于抑制这两种复合物的药物要么正在进行临床试验，要么已被批准用于治疗癌症（一种肌肉萎缩疾病），我们确定研究 mTORC1-蛋白酶体组合抑制对骨骼肌质量和健康的影响是一个需要研究的关键领域。