TY - JOUR
T1 - Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast
AU - Fei, Weihua
AU - Shui, Guanghou
AU - Gaeta, Bruno
AU - Du, Ximing
AU - Kuerschner, Lars
AU - Li, Peng
AU - Brown, Andrew J.
AU - Wenk, Markus R.
AU - Parton, Robert G.
AU - Yang, Hongyuan
PY - 2008/2/11
Y1 - 2008/2/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=39049151385&partnerID=8YFLogxK
U2 - 10.1083/jcb.200711136
DO - 10.1083/jcb.200711136
M3 - Article
C2 - 18250201
AN - SCOPUS:39049151385
SN - 0021-9525
VL - 180
SP - 473
EP - 482
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -