A role for phosphatidic acid in the formation of "supersized" lipid droplets

Fei, Weihua, Shui, Guanghou, Zhang, Yuxi, Krahmer, Natalie, Ferguson, Charles, Kapterian, Tamar S., Lin, Ruby C., Dawes, Ian W., Brown, Andrew J., Li, Peng, Huang, Xun, Parton, Robert G., Wenk, Markus R., Walther, Tobias C. and Yang, Hongyuan (2011) A role for phosphatidic acid in the formation of "supersized" lipid droplets. Plos Genetics, 7 7: e1002201.1-e1002201.11. doi:10.1371/journal.pgen.1002201

Author Fei, Weihua
Shui, Guanghou
Zhang, Yuxi
Krahmer, Natalie
Ferguson, Charles
Kapterian, Tamar S.
Lin, Ruby C.
Dawes, Ian W.
Brown, Andrew J.
Li, Peng
Huang, Xun
Parton, Robert G.
Wenk, Markus R.
Walther, Tobias C.
Yang, Hongyuan
Title A role for phosphatidic acid in the formation of "supersized" lipid droplets
Journal name Plos Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2011-07
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002201
Open Access Status DOI
Volume 7
Issue 7
Start page e1002201.1
End page e1002201.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing ‘‘supersized’’ LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of ‘‘supersized’’ LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism. 
Keyword Congenital Generalized Lipodystrophy
Saccharomyces Cerevisiae
Adipocyte Differentiation
Endoplasmic Reticulum
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article no. e1002201

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
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