Mutations in the seipin complex components Fld1 and Ldb16 result in the loss of lipid droplet identity and phospholipid packing defects, revealing a role of this complex in the stabilization of ER–lipid droplet contact sites.

Lipid droplets (LDs) and peroxisomes are ubiquitous organelles with central roles in eukaryotic cells. Although the mechanisms involved in biogenesis of these organelles remain elusive, both seem to require the endoplasmic reticulum (ER). Here we show that in yeast the ER budding of these structurally unrelated organelles has remarkably similar requirements and involves cooperation between Pex30 and the seipin complex. In the absence of these components, budding of both LDs and peroxisomes is inhibited, leading to the ER accumulation of their respective constituent molecules, such as triacylglycerols and peroxisomal membrane proteins, whereas COPII vesicle formation remains unaffected. This phenotype can be reversed by remodeling ER phospholipid composition highlighting a key function of these lipids in organelle biogenesis. We propose that seipin and Pex30 act in concert to organize membrane domains permissive for organelle budding, and that may have a lipid composition distinct from the bulk ER.

Lipid droplets (LDs) are essential organelles for cellular energy homeostasis, but how metabolic cues are integrated in their life cycle is unclear. Teixeira et al. find that two protein isoforms, Ldo16 and Ldo45, differentially regulate LD dynamics under nutrient-rich and -deprived conditions, linking energy metabolism and storage.