The change of intracellular zinc distribution after strong acid challenge

Zinc (Zn²⁺) is stored in the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and zinc-binding proteins. The acidity of the microenvironment affects the binding between zinc and proteins in which zinc become free or loosely bound. In this study, when cells were treated with an acidic medium, we started seeing free zinc 'hot spots' or zincosomes where we found bright zinc fluorescence. The rising free zinc quickly across whole cells with both intensity and distribution were pH-dependent. Interestingly, the nucleus was more sensitive to acidic treatment as the increase of nuclear zinc was faster and higher than the increase of cytosolic zinc. In addition, we re-cultured strong acid-challenged cells in a normal medium. Comparing to the control, these cells exhibited multiple zinc 'hot spots' beside the nucleus, suggesting that free zinc became more extensively distributed. To investigate further the function of zinc in cell shaping and morphological changes, we categorized strong acid-challenged cells into different shapes and found that the proportion of each cell shape had changed after the acid challenge. These acid-induced changes of the cell shape percentage were partially reversed by the reduction of zinc, suggesting that zinc participated in directing the cell shapes and morphologies during cell growth. Our findings reveal that acidic pH affects the dynamics of cellular zinc by making zinc more accessible to cellular compartments and zinc-binding proteins, which provided new insights into understanding the cellular behavior and the function of zinc in it.