A multifunctional fluorescent probe for tracking SO2 fluctuation between mitochondria and endoplasmic reticulum in living cells and zebrafish

The sulfur dioxide (SO2)-associated dynamic interplay between mitochondria (Mito) and endoplasmic reticulum (ER) is essential for intracellular homeostasis regulation. Visualizing such organelles interactions can help elucidate basic pathogenesis. However, it is hampered by challenges in developing quick response, remarkable sensitivity and high selectivity within a single fluorescent probe for simultaneous and distinct tracking of their crosstalk. Herein, we engineered a SO2-responsive Mito-ER dual-targeted fluorescent probe (MER-SO2) for dual-color visualization of Mito (red fluorescence) and ER (blue fluorescence) in living cells and in vivo. Under physiological conditions, the benzopyranium cationic structure in MER-SO2 could target Mito, following fast response to SO2 (5 s), which converted to a neutral structure, targeting to ER emitting blue fluorescence via functional fluorescence conversion. Probe MER-SO2 also displayed high sensitivity, favourable specificity (against 24 types of non-targeting analytes). Importantly, such a high-performance probe allowed in-situ and dynamic tracking of Mito-ER interactions in Mito-dysfunction living cells and zebrafish via co-localization. Furthermore, the probe enabled accurate detection of sulphite in food with recoveries rate (96-100%), and incorporation into an agarose-based portable device for SO2 assay. Taken together, this initial SO2-responsive probe represents a promising tool for discriminative tracking of functional Mito-ER interactions in living systems and holds great potential in many other fields such as food engineering.