Selective detection of lipophagy with a highly specific lipid droplet probe

Lipophagy, the autophagic degradation of lipid droplets (LDs) by lysosomes, is an important route for maintaining LD homeostasis. Tools for lipophagy detection facilitate research in LD biology. Herein, we report LD-Blue, a highly specific LD probe, for tracking dynamic formation of LDs and detection of lipophagy. Upon lipophagy, LD-Blue chaperoning host LDs is delivered into lysosomes. By using the co-localization co-efficiency of LD-Blue and LysoTracker Red as the readout of lipophagy, we observed lipophagy induced by serum deprivation but not acute nutrient starvation as well as lipophagy inhibition by chloroquine and Bafilomycin A1. With the established fidelity of the LD-Blue-based co-localization assay for lipophagy, monensin is identified to be a potent inducer of lipophagy.