Visualizing changes in mitochondrial Mg ²⁺ during apoptosis with organelle-targeted triazole-based ratiometric fluorescent sensors†

Abstract

Targeted ratiometric fluorescent sensors enable visualization of Mg ²⁺ dynamics in mitochondria, revealing an increase in free Mg ²⁺ in early stages of apoptosis.

Abstract

Magnesium is one of the most abundant metals in cells and is essential for a wide range of cellular processes. Magnesium imbalance has been linked to a variety of diseases, but the scarcity of sensors suitable for detection of Mg ²⁺ with subcellular resolution has hampered the study of compartmentalization and mobilization of this ion in the context of physiological and pathological processes. We report herein a family of fluorescent probes for targeted detection of free Mg ²⁺ in specific intracellular organelles, and its application in the study of programmed cell death. The new sensors feature a triazole unit that plays both structural and electronic roles by serving as an attachment group for targeting moieties, and modulating a possible internal charge transfer process for ratiometric ion sensing. A probe decorated with an alkylphosphonium group was employed for the detection of mitochondrial Mg ²⁺ in live HeLa cells, providing the first direct observation of an increase in free Mg ²⁺ levels in this organelle in the early stages of Staurosporine-induced apoptosis.

Notes

†Electronic supplementary information (ESI) available: Experimental details, metal selectivity plots, determination of apparent dissociation constants, fluorescence microscopy co-localization analysis, and supporting figures. See DOI: 10.1039/c5sc02442k