title: Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER.
abstract: Close contacts between organelles, often called membrane contact sites (MCSs), are regions where lipids are exchanged between organelles. Here, we identify a novel mechanism by which cells promote phospholipid exchange at MCSs. Previous studies have shown that phosphatidylserine (PS) synthase activity is highly enriched in portions of the endoplasmic reticulum (ER) in contact with mitochondria. The objective of this study was to determine whether this enrichment promotes PS transport out of the ER. We found that PS transport to mitochondria was more efficient when PS synthase was fused to a protein in the ER at ER-mitochondria contacts than when it was fused to a protein in all portions of the ER. Inefficient PS transport to mitochondria was corrected by increasing tethering between these organelles. PS transport to endosomes was similarly enhanced by PS production in regions of the ER in contact with endosomes. Together, these findings indicate that PS production at MCSs promotes PS transport out of the ER and suggest that phospholipid production at MCSs may be a general mechanism of channeling lipids to specific cellular compartments.
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Muthukumar
authors.initials: M
authors.lastname: Kannan
authors.affiliation: Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, VA 22908.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Li-Ka
authors.initials: LK
authors.lastname: Liu
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Vineet
authors.initials: V
authors.lastname: Choudhary
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 prinzw@helix.nih.gov.
authors.forename: William A
authors.initials: WA
authors.lastname: Prinz
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D016695:Glycosyltransferases / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D050155:Lipogenesis / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000201:enzymology; D010718:Phosphatidylserines / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C490519:CHO1 protein, S cerevisiae; D010718:Phosphatidylserines; D029701:Saccharomyces cerevisiae Proteins; D016695:Glycosyltransferases; C412464:PssA protein, Rhizobium leguminosarum; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase
keywords: endoplasmic reticulum; lipid biochemistry; lipid transfer proteins; lipid transport; mitochondria; phosphatidylethanolamine; phosphatidylserine synthase; phospholipids/trafficking