Tethering Fat: Tethers in Lipid Droplet Contact Sites

Lipid droplets (LDs) are central hubs in cellular lipid handling. They serve as lipid storage organelles and are involved in neutral lipid biosynthesis and breakdown as well as in the production of phospholipids and sterols. For communication with other organelles, LDs are heavily engaged in contact sites. The molecular basis of these structures is formed by proteins or protein complexes termed tethers, which attach partner organelles to the surface of LDs. Here, we describe the structural and functional characteristics of recently identified LD tethers. Intriguingly, these LD tethers have additional features, such as the structural capacity to form tri-organellar contacts, domains specialized for interorganellar bulk lipid transfer, and connections to specific lipid metabolism enzymes, which might collectively contribute to the key role of LDs in cellular lipid flux.