Metal pollution has been identified as a global threat. The toxic mechanisms of metals are still unclear, and each metal has its own unique toxicity and mechanism. Elucidating the different subcellular toxicities of metals is essential for understanding their overall cytotoxicity and health protection. In this study, we for the first time applied bioimaging to investigate the subcellular behaviors of inorganic Hg, methylmercury (MeHg), Zn and Cu in zebrafish cells. The dynamic monitoring of pH (lysosomal pH and cellular pH) and the mapping of pH distribution during metal exposure were realized for the first time. Our results showed that inorganic Hg, MeHg and Zn reduced the lysosomal pH, but with different mechanisms. Inorganic Hg and Zn induced more lysosomes, and lysosomes were enlarg...[ Read more ]

Metal pollution has been identified as a global threat. The toxic mechanisms of metals are still unclear, and each metal has its own unique toxicity and mechanism. Elucidating the different subcellular toxicities of metals is essential for understanding their overall cytotoxicity and health protection. In this study, we for the first time applied bioimaging to investigate the subcellular behaviors of inorganic Hg, methylmercury (MeHg), Zn and Cu in zebrafish cells. The dynamic monitoring of pH (lysosomal pH and cellular pH) and the mapping of pH distribution during metal exposure were realized for the first time. Our results showed that inorganic Hg, MeHg and Zn reduced the lysosomal pH, but with different mechanisms. Inorganic Hg and Zn induced more lysosomes, and lysosomes were enlarged by Zn and shrunk by Cu. MeHg and Cu were found to reduce the mitochondrial respiratory function and membrane potential, respectively. Our results showed that lipid droplets may potentially play a role in inorganic Hg detoxification. We demonstrated that Zn was accumulated in lysosomes (76.5%) after entering the cells, and diffused to mitochondria when the concentration increased. After entering the cells, Cu was combined with glutathione and accumulated in the mitochondria (71.4%) to produce toxicity, and then further transported to lysosomes (58.6%) and eliminated. Besides, Cu reduced the uptake of Zn. Our study provided a novel method and insight into the cytotoxicity of metals.