A Mitochondria-Targeted Dye for Investigating Mo Mineral Powder Induced Cytotoxicity through SIM Super-Resolution Imaging

Heavy metal substances are known to do great harm to human beings. However, the mechanism of heavy-metal-induced toxicity at the cellular level is currently unclear. In this study, we developed a series of mitochondria-targeted fluorescence probes (KRhs) to explore the structural and environmental changes in mitochondria upon the treatment of molybdenum mineral powders by using SIM super-resolution imaging. These probes are designed by tuning the lengths of alkyl chains within a NIR xanthene dye to strengthen the self-assembly characteristics, thereby optimizing the targeting stability toward mitochondria and the signal-to-noise ratio of imaging. We applied KRh-C16 for super-resolution imaging of cells treated with various molybdenum (Mo) mineral powders and found the morphology changes of a single mitochondrion during molybdenum-induced autophagy with high-resolution imaging. We further identified the generation of reactive oxygen species during molybdenum damage. These results help us to understand the toxicity mechanism of heavy metal powders in the mining industry. Generally, this study provides a promising tool and technique for investigating mitochondria-related cytotoxicity.