title: A role for phosphatidic acid in the formation of "supersized" lipid droplets.
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.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Weihua
authors.initials: W
authors.lastname: Fei
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Natalie
authors.initials: N
authors.lastname: Krahmer
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.forename: Tamar S
authors.initials: TS
authors.lastname: Kapterian
authors.forename: Ruby C
authors.initials: RC
authors.lastname: Lin
authors.forename: Ian W
authors.initials: IW
authors.lastname: Dawes
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Xun
authors.initials: X
authors.lastname: Huang
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Tobias C
authors.initials: TC
authors.lastname: Walther
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
mesh_terms: D042541:Intracellular Space / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D015388:Organelles / Q000235:genetics / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: C527368:Fld1 protein, S cerevisiae; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; C483858:phosphatidylethanolamine