Jack of all trades – the lipid droplet organization (LDO) proteins are multifunctional organelle surface receptors

The literature on the lipid droplet organization (LDO) proteins Ldo16 and Ldo45 reads like a guided tour through the lipid droplet life cycle. Both yeast Ldo16/45 and their metazoan counterparts, the LDAF1/promethin proteins, were originally identified based on their connection to the lipodystrophy protein seipin, a key player in lipid droplet biogenesis. Mechanistic follow-up studies support a role of LDAF1/LDO as conserved integral component of the seipin lipid droplet biogenesis complex. However, at the same time, additional LDO functions beyond lipid droplet formation were identified in yeast. Together with Vac8, Ldo16/45 act as tethers for formation of vacuole lipid droplet (vCLIP) contact sites, structures that are crucial for lipid droplet breakdown via microautophagy during glucose starvation. Ldo45 additionally recruits the lipid transfer protein Pdr16 to vCLIP. Furthermore, Ldo16 was identified as a central player in the process of actomyosin-based lipid droplet motility, by acting as a receptor for the myosin adaptor protein Ldm1. Based on these findings, we suggest an overarching molecular role of the LDO proteins as multifunctional lipid droplet surface receptors that are optimized to coordinate the different aspects of the lipid droplet life cycle through an interplay with different effector proteins.