Significance
Mobile zinc plays important roles in mammalian physiology. Understanding
the action of mobile zinc requires tools to follow it
within and between live cells. Zinc-selective fluorescent probes
offer a facile means for detecting such mobile zinc, but small
molecules constructed to perform this task typically have an unpredictable
cellular distribution. Subtle changes in chemical structure
can radically alter subcellular localization. To overcome this
challenge, we installed a chemical unit to direct the sensor specifically
to mitochondria and discovered that tumorigenic cells
lose their ability to accumulate mobile zinc within these organelles.
To carry out this work, we devised a reaction-based sensor
that undergoes zinc-mediated chemistry, converting a nonfluorescent
molecule into one that emits brightly and avoiding
undesired sequestration in endo/lysosome.