The transport of protein aggregates to the vacuole suggests a role for lipid droplets in waste disposal in Saccharomyces cerevisiae

Lipid droplets (LDs) are organelles found in all eukaryotic cells, yet their contribution toward proteostasis is still poorly understood. In this study, we demonstrate that LDs in the model organism Saccharomyces cerevisiae function as transporters to which cytosolic protein aggregates attach for transport to the vacuole for degradation. With the help of chaperones and the yeast prion Rnq1, serving as an aggregation model, and using techniques such as live-cell imaging, super-resolution microscopy, electron microscopy, and biochemical analyses, we demonstrate that protein aggregates bind to LDs, are transported through the cytoplasm, and are ultimately transferred to the insoluble protein deposit (IPOD) on the vacuole surface. The efficiency of this process is highly dependent on the lipid composition of the LDs, with triacylglycerols identified as key determinants for aggregate docking. In LD-deficient cells, we observed severe fragmentation of the aggregates and a complete loss of IPOD, whereas stimulation of LD formation significantly increased the size of IPOD and vacuolar import activity. Overall, our results expand the understanding of cellular protein quality control and link lipid metabolism research to the regulation of protein aggregation. The evidence that LDs act as 'garbage trucks' transporting protein aggregates to the vacuole reveals a new interface between proteostasis and lipid metabolism that could also be significant in higher eukaryotes.