Defining Cancer Cell Bioenergetic Profiles Using a Dual Organelle-Oriented Chemosensor Responsive to pH Values and...

Cell fate is largely shaped by combined activity of different types of organelles, which often feature functionally critical parameters that succumb to pathological inducers. We herein report the analysis of cell bioenergetic profiles with a dual organelle-oriented chemosensor (RC-AMI), partitioning in mitochondria to give blue fluorescence and in lysosomes to give red fluorescence. Responsive to lysosomal pH and mitochondrial transmembrane potential (ΔΨ_m), two parameters crucial to cell bioenergetics, RC-AMI enables dual colored reporting of lysosomal acidity and ΔΨ_m, revealing upregulated ΔΨ_m and imbalance dramatically shifted favoring ΔΨ_m over lysosomal acidity in cancer cells whereas the tendency is reversed in starved cells. Complementing classical homo-organelle-specific sensors, this dual organelle-oriented and fluorescently responsive probe offers a new tool to detect imbalance between lysosomal acidity and mitochondrial ΔΨ_m, an index critical for cancer bioenergetics.