The architecture and mechanism of lipid transfer at interfaces between lipid droplets
Iva Ganeva (University of Bern, Switzerland)
Lipid droplets (LDs) are intracellular organelles responsible for regulated storage and release of neutral lipids. LDs feature a neutral lipid core enclosed by a phospholipid monolayer and surface proteins involved in lipid metabolism. The protein Cidec is crucial for LD enlargement and accumulates at interfaces between LDs where it facilitates directional neutral lipid transfer from the smaller to the larger LD. Deciphering the structure of the LD-LD interface is key in understanding the molecular mechanism of lipid transfer. We use live cell imaging and electron cryo-tomography of human cells to visualize interfaces between LDs and understand the mechanism of lipid transfer directly inside cells. Furthermore, by biochemical reconstitutions using recombinant Cidec and various artificial membrane systems, we aim at uncovering the minimal machinery for interface architecture and lipid transfer function. Our current model is that lipid transfer occurs through largely intact monolayers at an interface which resembles an organelle contact site. We hypothesise that this process is facilitated by the ability of Cidec to induce lipid packing defects into the monolayers, thereby making them permeable for neutral lipids.