Chemical probe profiles live-cell organelle activity, adds to understanding of lysosome dynamics Structured illumination microscopy imaging showing subcellular probe labeling of functionally active enzymes called cathepsins, in the lysosome. The green fluorescence stems from probe-labeled enzymes, and the red fluorescence is from a fluorescent antibody specific for lysosome membranes. Probe-labeling fluorescence is surrounded by the antibody fluorescence, showing lysosomal localization. A team of scientists from Pacific Northwest National Laboratory synthesized a chemical activity-based probe (ABP) that can provide new information about how living cells function. The new ABP is designed to enter a living cell without interacting with anything until it enters a specific organelle: the lysosome. This proof-of-concept ABP then labels only functionally active enzymes called cathepsins, which are cysteine proteases, in the lysosome. Using proteomics and super-resolution microscopy to view these labeled enzymes, the scientists now are able to see organellar activity. Their work, which demonstrates the ability to manipulate chemistry to better understand biology, has been published in Angewandte Chemie International Edition. Why It Matters: Found throughout mammalian cells, lysosomes are important for cell stability as the “housekeepers,” disposing of unnecessary or nonworking components. They also play a role in many different diseases, among them cancer and
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