Journal Club

Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins

Science; Sep 2022; Vol 378, Issue 6615

LYSET helps load lysosomes

Lysosomes are major degradative compartments within the cell, and their dysfunction results in both rare and common disorders. Certain viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hijack lysosomes to gain entry into the cell and start their destructive infection cycle. Richards et al. identified a small protein named LYSET that is critical for proper lysosomal function. In cells lacking LYSET, the trafficking of enzymes to the lysosomes was severely disrupted resulting in the accumulation of undigested material in the lysosome. Independently, Pechincha et al. identified LYSET as being selectively essential when cells feed on extracellular proteins. Cancer cells commonly rely on extracellular proteins to provide amino acids. LYSET helped to anchor N-acetylglucosamine-1-phosphotransferase in Golgi membranes for tagging enzymes with the lysosomal trafficking signal mannose-6-phosphate. Without LYSET, lysosomes were depleted of catabolic enzymes, losing their ability to digest extracellular proteins.