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 of 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.