Recent work has highlighted the fact that lysosomes are a critical signaling hub of metabolic processes, providing fundamental building blocks crucial for anabolic functions. How lysosomal functions affect other cellular compartments is not fully understood. Here, we find that lysosomal recycling of the amino acids lysine and arginine is essential for proper ER quality control through the UPR^ER. Specifically, loss of the lysine and arginine amino acid transporter LAAT-1 results in increased sensitivity to proteotoxic stress in the ER and decreased animal physiology. We find that these LAAT-1–dependent effects are linked to glycine metabolism and transport and that the loss of function of the glycine transporter SKAT-1 also increases sensitivity to ER stress. Direct lysine and arginine supplementation, or glycine supplementation alone, can ameliorate increased ER stress sensitivity found in laat-1 mutants. These data implicate a crucial role in recycling lysine, arginine, and glycine in communication between the lysosome and ER.

最近的研究强调了这样一个事实：溶酶体是代谢过程的关键信号中心，为合成代谢功能提供了至关重要的基本构建模块。溶酶体功能如何影响其他细胞区室尚不完全清楚。在这里，我们发现氨基酸赖氨酸和精氨酸的溶酶体回收对于通过 UPR ^ER进行正确的 ER 质量控制至关重要。具体来说，赖氨酸和精氨酸转运蛋白 LAAT-1 的缺失会导致 ER 中蛋白毒性应激的敏感性增加，并导致动物生理机能下降。我们发现这些 LAAT-1 依赖性效应与甘氨酸代谢和转运有关，并且甘氨酸转运蛋白 SKAT-1 功能的丧失也会增加对 ER 应激的敏感性。直接补充赖氨酸和精氨酸，或单独补充甘氨酸，可以改善laat-1突变体中发现的内质网应激敏感性增加。这些数据表明赖氨酸、精氨酸和甘氨酸的回收在溶酶体​​和内质网之间的通讯中发挥着至关重要的作用。