A Fluorogenic Inhibitor of the Mitochondrial Calcium Uniporter. Issue 6 (9th January 2023)

• Record Type: Journal Article
• Authors: Huang, Zhouyang; MacMillan, Samantha N.; Wilson, Justin J.
• Is Part Of: Angewandte Chemie international edition. Volume 62:Issue 6(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-09
• Subjects: Bioinorganic Chemistry -- Fluorescent Probes -- Mitochondrial Calcium Uniporter -- Prodrugs -- Ruthenium; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202214920
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Inhibitors of the mitochondrial calcium uniporter (MCU) are valuable tools for studying the role of mitochondrial Ca 2+ 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. Abstract : RuOCou is a novel fluorogenic inhibitor of the mitochondria calcium uniporter (MCU). Its aquation‐activated increase in MCU‐inhibitory activity can be visualized directly by a concomitant enhancement in fluorescence intensity.