Genome-wide screening for novel gene products that regulate the cellular dynamics of lipid droplets in Saccharomyces cerevisiae

During recent years, scientific research on lipid droplet (LD) cell biology has made significant progress. It has been recognized that LDs are not only intracellular organelles specialized for the storage of lipids but also dynamic in nature. LDs are comprised of a neutral lipid core of triacylglycerols (TAG) and sterol esters (SE), which are surrounded by a monolayer of phospholipids with proteins embedded. Formation of LDs is proposed to occur in the endoplasmic reticulum (ER). However, there are several fundamental questions relating to the biology of LDs. For instance, how newly synthesized TAG is formed in the core of the LDs,what factors control the shape, size and movement of LDs and how do LDs grow? With the purpose to study cellular dynamic of LDs in a model organism, the yeast Saccharomyces cerevisiae, the aim of this research is to identify the novel genes/gene products that regulate the dynamic of LDs, in particular, the localization and the size of LDs.By screening the entire collection of essential gene mutants in yeast, we found 32 mutants which displayed a defective LD morphology. Interestingly, a number of mutants which are defective in sterol biosynthesis exhibited an accumulation of large amounts of squalene and clustering of LDs. Further analyses established an association between squalene and LD clustering. This work also provides evidence that CK2 Protein Kinase is involved in maintaining LD size by regulating mRNA level of CDS1, which then affects the phosphatidic acid (PA) and TAG contents. Together, these findings imply that an increase in the level of neutral lipids such as squalene, TAG or SE may be sufficient to trigger LD aggregation, but not LD fusion to form supersized LDs. Our results thus indentified novel proteins and schemes that regulate the cell biology of lipid droplets