Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast

TLDR

Lipid droplets are essential organelles implicated in cell biology and human disease. The authors screened ~4,700 yeast mutants for abnormalities in LD number and morphology, identifying 17 few‑LD (fld) and 116 many‑LD (mld) mutants. The fld1 mutant, caused by deletion of YLR404W, produces enlarged LDs with increased fusion activity, and expression of human seipin rescues these defects; lipid profiling shows altered phospholipid acyl chains, indicating a conserved role of seipin in phospholipid metabolism and LD formation relevant to human adipogenesis.

Abstract

Lipid droplets (LDs) are emerging cellular organelles that are of crucial importance in cell biology and human diseases. In this study, we present our screen of ∼4,700 Saccharomyces cerevisiae mutants for abnormalities in the number and morphology of LDs; we identify 17 fld (few LDs) and 116 mld (many LDs) mutants. One of the fld mutants (fld1) is caused by the deletion of YLR404W, a previously uncharacterized open reading frame. Cells lacking FLD1 contain strikingly enlarged (supersized) LDs, and LDs from fld1Δ cells demonstrate significantly enhanced fusion activities both in vivo and in vitro. Interestingly, the expression of human seipin, whose mutant forms are associated with Berardinelli-Seip congenital lipodystrophy and motoneuron disorders, rescues LD-associated defects in fld1Δ cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1Δ cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis.