A Fluorogenic Inhibitor of the Mitochondrial Calcium Uniporter

Inhibitors of the mitochondrial calcium uniporter (MCU) are valuable tools for studying the role of mitochondrial Ca2+ in various pathophysiological conditions. In this study, a new fluorogenic MCU inhibitor, RuOCou, is presented. This compound is an analogue of the known MCU inhibitor Ru265 that contains fluorescent axial coumarin carboxylate ligands. Upon aquation of RuOCou and release of the axial coumarin ligands, a simultaneous increase in its MCU-inhibitory activity and fluorescence intensity is observed. The fluorescence response of this compound enabled its aquation to be monitored in both HeLa cell lysates and live HeLa cells. This fluorogenic prodrug represents a potential theranostic MCU inhibitor that can be leveraged for the treatment of human diseases related to MCU activity.

Automated summary

In this study, a new fluorogenic mitochondrial calcium uniporter (MCU) inhibitor, RuOCou, is introduced. This compound exhibits both increased MCU-inhibitory activity and fluorescence intensity after aquation. By monitoring its fluorescence response, the aquation of RuOCou can be observed in HeLa cell lysates and live HeLa cells. This fluorogenic prodrug shows potential as a theranostic MCU inhibitor for the treatment of human diseases associated with MCU activity.