Lipid droplets store lipids and thus serve both as an energy reservoir and as a source of building blocks for the organellar membrane systems. Therefore, lipid droplet biology depends on tight communication with other organelles. One important way of interorganellar communication is by formation of contact sites, places where the surfaces of different organelles are actively positioned in very close proximity to each other. We can detect distinct subpopulations of lipid droplets at the surface of virtually all other organelles in S. cerevisiae that appear to be tethered to their surrounding membranes. 

We find that a lipid droplet subpopulation positioned adjacent to the NVJ, the contact site between the nucleus and the vacuole/lysosome, is equipped with a unique surface proteome. In an attempt to identify molecular factors determining the identity of these lipid droplets, we screened ~6000 mutants for mislocalization of a subpopulation marker, Pdr16, and identified Ldo45 (lipid droplet organization protein of 45 kDa) as a crucial targeting determinant. Ldo45 is derived from a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). Ldo proteins are evolutionary conserved proteins that cooperate with the contact site component seipin, and determine lipid droplet identity by defining their positioning and surface protein composition. Our results suggest a contact site based mechanism to imprint functional specialization of organelles, opening a door to deeper understanding of metabolic decisions in the cell.