A metabolically controlled contact site between vacuoles and lipid droplets in yeast.

The lipid droplet (LD) organization proteins Ldo16 and Ldo45 affect multiple aspects of LD biology in yeast. They are linked to the LD biogenesis machinery seipin, and their loss causes defects in LD positioning, protein targeting, and breakdown. However, their molecular roles remained enigmatic. Here, we report that Ldo16/45 form a tether complex with Vac8 to create vacuole lipid droplet (vCLIP) contact sites, which can form in the absence of seipin. The phosphatidylinositol transfer protein (PITP) Pdr16 is a further vCLIP-resident recruited specifically by Ldo45. While only an LD subpopulation is engaged in vCLIPs at glucose-replete conditions, nutrient deprivation results in vCLIP expansion, and vCLIP defects impair lipophagy upon prolonged starvation. In summary, Ldo16/45 are multifunctional proteins that control the formation of a metabolically regulated contact site. Our studies suggest a link between LD biogenesis and breakdown and contribute to a deeper understanding of how lipid homeostasis is maintained during metabolic challenges.

CG32803 is the fly homolog of LDAF1 and influences lipid storage in vivo.

The Seipin protein is a conserved key component in the biogenesis of lipid droplets (LDs). Recently, a cooperation between human Seipin and the Lipid droplet assembly factor 1 (LDAF1) was described. LDAF1 physically interacts with Seipin and the holocomplex safeguards regular LD biogenesis. The function of LDAF1 proteins outside mammals is less clear. In yeast, the lipid droplet organization (LDO) proteins, which also cooperate with Seipin, are the putative homologs of LDAF1. While certain functional aspects are shared between the LDO and mammalian LDAF1 proteins, the relationship between the proteins is under debate. Here, we identify the Drosophila melanogaster protein CG32803, which we re-named to dmLDAF1, as an insect member of this protein family. dmLDAF1 decorates LDs in cultured cells and in vivo and the protein is linked to the fly and mouse Seipin proteins. Altering the dmLDAF1 abundance affects LD size, number and overall lipid storage amounts. Our results suggest that the LDAF1 proteins thus fulfill an evolutionarily conserved function in the biogenesis and biology of LDs.

Come a little bit closer! Lipid droplet-ER contact sites are getting crowded.

Not so long ago, contact sites between the endoplasmic reticulum (ER) and lipid droplets (LDs) were largely unexplored on a molecular level. In recent years however, numerous proteins have been identified that are enriched or exclusively located at the interfaces between LDs and the ER. These comprise members of protein classes typically found in diverse types of contacts, such as organelle tethers and lipid transfer proteins, but also proteins that have no similarities to known contact site machineries. This structurally heterogeneous group of contact site residents might be required to fulfill unique aspects of LD-ER contact biology, such as de novo LD biogenesis, and maintenance of lipidic connections between LDs and ER. Here, we summarize the current knowledge on the molecular components of this special organelle contact site, and discuss their features and functions.