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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.22.609247
preprint
1
Article
Leveraging Chlorination-Based Mechanism for Resolving Subcellular Hypochlorous Acid
Tang Fung Kit
Tucker Lawrence
Nadiveedhi Maheshwara Reddy
Hladun Colby
Morse Jared
Ali Mahnoor
Payne Noah
Schmidt Matthias
Leung Kaho
23 8 2024
2024.08.22.609247https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.22.609247
nihpp-2024.08.22.609247.pdf
Abstract

Hypochlorous acid (HOCl) is crucial for pathogen defense, but an imbalance in HOCl levels can lead to tissue damage and inflammation. Existing HOCl indicators employ an oxidation approach, which may not truly reveal the chlorinative stress environment. We designed a suite of indicators with a new chlorination-based mechanism, termed HOClSense dyes, to resolve HOCl in sub-cellular compartments. HOClSense dyes allow the visualization of HOCl with both switch-on and switch-off detection modes with diverse emission colors, as well as a unique redshift in emission. HOClSense features a minimalistic design with impressive sensing performance in terms of HOCl selectivity, and our design also facilitates functionalization through click chemistry for resolving subcellular HOCl. As a proof of concept, we targeted plasma membrane and lysosomes with HOClSense for subcellular HOCl mapping. With utilizing HOClSense, we discovered the STING pathway-induced HOCl production and the abnormal HOCl production in Niemann-Pick diseases. To the best of our knowledge, this is the first chlorination-based HOCl indicator series for resolving subcellular HOCl.
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