Lysosomal recycling of amino acids through LAAT-1 impacts ER quality control.
Description
The homeostatic relationship between the lysosome and other organelles is often linked to the role of lysosomes in autophagic degradation of damaged cellular compartments (Khaminets et al., 2015; Koyano et al., 2014; Narendra et al., 2008; Schuck et al., 2014). However, recent work has highlighted the critical role lysosomes serve as the central signaling hub of metabolic processes. Through these processes, the lysosome serves as a major source of amino acids, sugars, lipids, and other fundamental building blocks, which are crucial for anabolic functions, especially those of the ER (Abu-Remaileh et al., 2017; Ballabio and Gieselmann, 2009; Platt et al., 2012). Here, we find that lysosomal recycling of the amino acids, lysine and arginine, are essential for proper ER quality control through UPRER. 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. Importantly, direct lysine and arginine supplementation can ameliorate increased ER stress sensitivity, implicating a crucial role in recycling lysine and arginine in communication between the lysosome and ER.