Reaction-based fluorescent sensor for investigating mobile Zn 2+ in mitochondria of healthy versus cancerous prostate cells

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.