Monitoring HS fluctuation during autophagic fusion of lysosomes and mitochondria using a lysosome-targeting fluorogenic probe.

Hydrogen sulfide (HS) plays a cytoprotective role during mitophagy by detoxifying superfluous reactive oxygen species (ROS), and its concentration fluctuates in this process. However, no work has been reported to reveal the variation in HS levels during autophagic fusion of lysosomes and mitochondria. Herein, we present a lysosome-targeted fluorogenic probe, named NA-HS, for real-time monitoring of HS fluctuation for the first time. The newly synthesized probe exhibits good selectivity and high sensitivity (detection limit of 23.6 nM). Fluorescence imaging results demonstrated that NA-HS could image exogenous and endogenous HS in living cells. Interestingly, the colocalization results revealed that the level of HS was upregulated after autophagy began because of the cytoprotective effect, and was finally gradually reduced during subsequent autophagic fusion. This work not only affords a powerful fluorescence tool to monitor the variations in HS levels during mitophagy, but also offers new insights into targeting small molecules for elaborating the complex cellular signal pathways.