Intra- and intercellular distribution of mitochondrial probes and changes after treatment with MDR modulators.

Fluorescent probes are currently used to evaluate the mitochondrial transmembrane potential in situ. However, in parallel experiments using the probes JC-1 and TMRM in different cell types (human astrocytes, HEp-2, Vero, KB, and HeLa cells), we found that the distribution of JC-1 and TMRM is highly variable not only in different cell types but also in different cells of the same cell type, a condition that has never been documented until our work. This phenomenon depends on a hidden, widespread multidrug resistance (MDR) phenotype that can be recognized only by comparative assays with MDR inhibitors (progesterone, verapamil, and cyclosporin A) and represents a serious risk of error in the evaluation of the mitochondrial potential.