Live cell imaging of lipid droplets: fluorescent chalcones as probes for lipophagy and lipid–mitochondria interactions

Lipid droplets are crucial organelles involved in cellular energy storage and metabolism, which is key in maintaining energy homeostasis through lipophagy. In this work, we successfully synthesized donor–acceptor chalcone derivatives (M1–M3) with improved photophysical characteristics, such as significant Stokes shifts and strong emission features. DFT and TDDFT calculations have been employed to evaluate the structure–property relationship of the chalcone derivatives. The molecules show excellent selectivity in staining lipid droplets in COS-7 cells and other cell lines. The molecule M1 was also further utilized to monitor verapamil-induced lipophagy. Using M1, we also demonstrate the link between lipid droplets and mitochondria during stress, emphasizing the significance of lipophagy in cellular energy balance and metabolism. These results not only shed light on the lipid metabolism but also have profound implications for researching and potentially treating metabolic diseases, underscoring the importance of our work in the field.