Leveraging Chlorination-Based Mechanism for Resolving Subcellular Hypochlorous Acid

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Cellular Biology

Background:

• Hypochlorous acid (HOCl) is vital for immunity but its dysregulation causes inflammation and tissue damage.
• Current HOCl detection methods rely on oxidation, potentially misrepresenting chlorinative stress.
• Accurate visualization of HOCl in sub-cellular compartments is needed to understand its biological roles.

Purpose of the Study:

• To develop novel indicators for sensitive and selective detection of HOCl in sub-cellular environments.
• To introduce a new chlorination-based sensing mechanism distinct from oxidation methods.
• To enable visualization of HOCl dynamics within specific organelles and cellular compartments.

Main Methods:

• Design and synthesis of a new series of HOCl indicators, termed HOClSense dyes.
• Utilizing a chlorination-based sensing mechanism for HOCl detection.
• Employing click chemistry for functionalization and targeting specific sub-cellular locations like plasma membrane and lysosomes.

Main Results:

• HOClSense dyes demonstrate switch-on/off detection modes with diverse emission colors and redshift.
• The indicators exhibit high selectivity for HOCl.
• Successful subcellular HOCl mapping in plasma membrane and lysosomes.
• Discovery of STING pathway-induced HOCl production and abnormal HOCl in Niemann-Pick diseases.

Conclusions:

• HOClSense represents the first chlorination-based indicator series for resolving sub-cellular HOCl.
• This new tool provides unprecedented insights into HOCl biology and pathology.
• The findings pave the way for understanding HOCl's role in immune response and diseases.