GENOME-WIDE SCREEN OF GENES THAT REGULATE LIPID DROPLET DYNAMICS IN SACCHAROMYCES CEREVISIAE

Abstract

Lipid droplets consist of a highly hydrophobic core of neutral lipids and are surrounded by a monolayer of phospholipids. They are associated with many devastating diseases. Several mammalian proteins have been shown to have an important role in lipid droplet biosynthesis, but many remain unidentified. In an effort to identify genes that regulate lipid droplet dynamics, I screened the entire collection of viable single-gene deletion yeast strains, and found 16 mutants with markedly reduced accumulation of lipid droplets and 117 mutants with increased accumulation of lipid droplets. Remarkably, cells lacking Ylr404wp, an ortholog of human lipodystrophy protein seipin, synthesized supersized lipid droplets. Moreover, lipid droplets of ylr404w cells demonstrated enhanced fusion both in vivo and in vitro. Phospholipid profiling showed that a shift from long-chain to medium/short-chain fatty acid incorporation into phospholipids occurs due to YLR404W deletion. This result may suggest that modulation of the synthesis of phospholipids is critical for lipid droplet assembly as well as adipogenesis.