The architecture of Cidec-mediated interfaces between lipid droplets

Abstract

Lipid droplets (LDs) are intracellular organelles responsible for storing surplus energy as neutral lipids. Their size and number vary enormously (1). In white adipocytes, they reach up to 100 {micro}m in size, occupying >90% of the cell. Cidec, which is strictly required for the formation of such large LDs, is concentrated at interfaces between adjacent LDs and facilitates the directional flux of neutral lipids from the smaller to the larger LD (2-7). However, the mechanism of lipid transfer is unclear, in part because the architecture of interfaces between LDs has remained elusive. Here we visualised interfaces between LDs by electron cryo-tomography (cryo-ET) and analysed the kinetics of lipid transfer by quantitative live fluorescence microscopy (FM). We show that transfer occurs through closely apposed intact monolayers, is slowed down by increasing the distance between the monolayers and follows exponential kinetics suggesting a pressure-driven mechanism. We thus propose that unique architectural features of LD-LD interfaces are mechanistic determinants of neutral lipid transfer.