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

摘要

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 (Delta Psi(m),), two parameters crucial to cell bioenergetics, RC-AMI enables dual colored reporting of lysosomal acidity and Delta Psi(m) revealing upregulated Delta Psi(m) and imbalance dramatically shifted favoring Delta Psi(m), over lysosomal acidity in cancer cells whereas the tendency is reversed in starved cells. Complementing classical homoorganelle-specific sensors, this dual organelle-oriented and fluorescently responsive probe offers a new tool to detect imbalance between lysosomal acidity and mitochondrial Delta Psi(m), an index critical for cancer bioenergetics.