Organelle-Directed Metabolic Glycan Labeling and Optical Tracking of Dysfunctional Lysosomes Thereof.

Metabolic glycan labeling (MGL) has been employed for diverse purposes, such as cell surface glycan imaging and tumor surface engineering. We herein reported organelle-specific MGL (OMGL) for selective tagging of the inner limiting membrane of lysosomes over the cell surface. This is operated via acidity-promoted accumulation of optical probes in lysosomes and bioorthogonal ligation of the trapped probes with 9-azidosialic acid (AzSia) metabolically installed on lysosomal membrane proteins. Overcoming the limitation of classical organelle probes to dissipate from stressed organelles, OMGL enables optical tracking of pH-elevated lysosomes in exocytosis and membrane-permeabilized lysosomes in different cell death pathways. Thus, OMGL offers a new tool to study lysosome biology.