Monitoring H2S fluctuation during autophagic fusion of lysosomes and mitochondria using a lysosome-targeting fluorogenic probe.

Hydrogen sulfide (H 2 S) 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 H 2 S levels during autophagic fusion of lysosomes and mitochondria. Herein, we present a lysosome-targeted fluorogenic probe, named NA-HS, for real-time monitoring of H 2 S 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 H 2 S in living cells. Interestingly, the colocalization results revealed that the level of H 2 S 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 H 2 S levels during mitophagy, but also offers new insights into targeting small molecules for elaborating the complex cellular signal pathways. The variation of H 2 S during autophagic fusion of lysosome and mitochondria was revealed by a lysosome-targeting fluorogenic probe. [Display omitted] • H 2 S fluctuation during mitophagy was revealed by a synthetic fluorescence probe. • The endogenous and exogenous H 2 S can be imaged with this fluorescence probe. • The level of H 2 S was revealed to upregulate and then reduced during mitophagy. [ABSTRACT FROM AUTHOR]