Title: A sugar sorting pathway directed bioorthogonal conjugation enables continual tracking of stressed organelles

Authors: Shoufa Han, Zhongwei, Xue  Enkang Zhang,  Jian Liu,  Jiahuai Han

Abstract:

Selective and continuous tracking of dynamic organelles are crucial for modern biology. We herein reported a ship‐in‐bottle strategy to tag lysosomes using strain‐promoted azide‐alkyne cycloaddition to couple a pH sensor (RC) with mannose‐6‐carboxylate (M6C) actively transported into lysosomes via cell sorting. Relative to classical acidotropic sensors prone to dissipate from lysosomes, in situ formed M6C‐RC is stably trapped in lysosomes without resort to lysosomal acidity, exhibiting "always‐on" blue fluorescence to pinpoint lysosomes and red‐to‐blue fluorescence ratios indicative of lysosomal pH. These advantages enable tracking of stressed lysosomes and discern of lysosomal pH changes in necrosis over apoptosis. The cell sorting‐mediated bioorthogonal tagging strategy offers a new route to track stressed organelles with disrupted physiological organelle‐probe affinity.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.201802972