LAAT-1 Is the Lysosomal Lysine/Arginine Transporter That Maintains Amino Acid Homeostasis

Abstract

Lysosomal Amino Acid Transporter Cystinosis is characterized by intralysosomal accumulation of free cystine, which results in age-dependent problems in the kidney, muscle, retina, and central nervous system. The disease-causing gene encodes a lysosomal cystine transporter. The most effective therapeutic agent for cystinosis, cysteamine, depletes lysosomal free cystine by converting it to cysteine and the mixed disulfide cysteine-cysteamine, which can then be exported from lysosomes as a lysine analog through a putative lysine/cationic amino acid transporter. Using an unbiased genetic screen for Caenorhabditis elegans mutants with increased accumulation of apoptotic cells or autophagosomes, Liu et al. (p. 351 ) now reveal the molecular identity of a lysosomal lysine/arginine transporter that plays a role in maintaining lysosome function and amino acid homeostasis and that can explain how cysteamine alleviates a lysosomal storage disease.