A mitochondria-targeted H2S-activatable fluorogenic probe for tracking hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury (HIRI) is the cause of postoperative hepatic dysfunction and failure, and even death. As an important biological effector molecule, hydrogen sulfide (H2S) of mitochondria as a gasotransmitter that is usually used to protect against acute HIRI injury. However, the exact relationship between HIRI and mitochondrial H2S remains tangled due to the lack of an effective analytical method. Herein, we have fabricated a mitochondria-targeted H2S-activatable fluorogenic probe (Mito-GW) to explore the stability of mitochondrial H2S and track the changes in mitochondrial H2S during the HIRI. By virtue of pyridinium electropositivity and its amphiphilicity, Mito-GW could accumulate in mitochondria. It goes through an analyte-prompted immolation when reacts with H2S, resulting in the releasing of the fluorophore (GW). Therefore, the extent of Mito-GW conversion to GW can be used to evaluate the changes of mitochondrial H2S level in living cells and tissues. As proof-of-principle, we have used Mito-GW to demonstrate the mitochondria H2S-levels increase and then decrease during HIRI in vitro and in vivo. Our research highlights the tremendous potential of Mito-GW as a mitochondrial H2S fluorogenic probe in elucidating the pathogenesis of HIRI, providing a powerful tool for promoting future research on hepatology.