Lipoprotein-mediated delivery of BODIPY-labeled sterol and sphingolipid analogs reveals lipid transport mechanisms in mammalian cells

•BODIPY-sterols and -sphingolipids can be targeted to late endosomes via lipoproteins.•These lipids can be metabolized by the same enzymes as corresponding natural lipids.•Their use has helped to unravel proteins involved in lipid efflux from late endosomes.

Lipids are often introduced into cell membranes directly from solvent or from lipophilic artificial carriers, such as cyclodextrins. A physiological lipid entry route into mammalian cells is via lipoprotein mediated uptake. In this review, we discuss the introduction of BODIPY-labeled sterol and sphingolipid analogs into mammalian cells via high- or low-density lipoproteins, and the novel findings made by using this strategy. Lipoprotein mediated delivery favors endocytic uptake and initial incorporation of the lipid into membranes of the endosomal compartments. This routing can therefore highlight physiological mechanisms of lipid entry into and exit from the endo-lysosomal membrane system. The underlying principles are of key importance for instance in controlling plasma cholesterol levels and in the development and regression of lysosomal lipid storage diseases. A common denominator for the BODIPY-labeled lipid analogs discussed in this review is that they were synthesized by late Robert Bittman, whose scientific impact radiates far beyond his lifework in organic chemistry.