title: New molecular mechanisms of inter-organelle lipid transport.
abstract: Lipids are precisely distributed in cell membranes, along with associated proteins defining organelle identity. Because the major cellular lipid factory is the endoplasmic reticulum (ER), a key issue is to understand how various lipids are subsequently delivered to other compartments by vesicular and non-vesicular transport pathways. Efforts are currently made to decipher how lipid transfer proteins (LTPs) work either across long distances or confined to membrane contact sites (MCSs) where two organelles are at close proximity. Recent findings reveal that proteins of the oxysterol-binding protein related-proteins (ORP)/oxysterol-binding homology (Osh) family are not all just sterol transporters/sensors: some can bind either phosphatidylinositol 4-phosphate (PtdIns(4)P) and sterol or PtdIns(4)P and phosphatidylserine (PS), exchange these lipids between membranes, and thereby use phosphoinositide metabolism to create cellular lipid gradients. Lipid exchange is likely a widespread mechanism also utilized by other LTPs to efficiently trade lipids between organelle membranes. Finally, the discovery of more proteins bearing a lipid-binding module (SMP or START-like domain) raises new questions on how lipids are conveyed in cells and how the activities of different LTPs are coordinated.
authors.affiliation: Institut de Pharmacologie Moléculaire & Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 660 route des lucioles, 06560 Valbonne, France drin@ipmc.cnrs.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drin
authors.affiliation: Biochemistry Department, University of Geneva, Science II, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Moser von Filseck
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Alenka
authors.initials: A
authors.lastname: Čopič
mesh_terms: D001692:Biological Transport; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D015388:Organelles / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism; D000098825:Oxysterol Binding Proteins
chemical_list: D010716:Phosphatidylinositols; D011987:Receptors, Steroid; D013261:Sterols; D000098825:Oxysterol Binding Proteins
keywords: ORP/Osh proteins; lipid counter-exchange; lipid gradient; lipid transfer proteins; membrane contact sites