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doi:10.1083/jcb.200711136
The Journal of Cell Biology
The Rockefeller University Press, 0021-9525 $30.00
© Fei et al.
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Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast



Weihua Fei1, Guanghou Shui1, Bruno Gaeta2, Ximing Du2, Lars Kuerschner3,4, Peng Li5, Andrew J. Brown2, Markus R. Wenk1, Robert G. Parton3,4, and Hongyuan Yang1,2

1 Department of Biochemistry, National University of Singapore, Singapore 117597, Republic of Singapore
2 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, New South Wales, Australia
3 Institute for Molecular Bioscience and 4 Centre for Microscopy and Microanalysis, University of Queensland, Brisbane 4072, Australia
5 Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China

Correspondence to Hongyuan Yang: h.rob.yang{at}unsw.edu.au

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 fld1{Delta} 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 fld1{Delta} cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1{Delta} cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis.

Abbreviations used in this paper: BSCL, Berardinelli-Seip congenital lipodystrophy; CGL, congenital generalized lipodystrophy; LD, lipid droplet; MRM, multiple reaction monitoring; PA, phosphatidic acid; SC, synthetic complete; SE, sterol ester; TAG, triacylglycerol; TEM, transmission EM.


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