title: Lipid topogenesis--35years on.
abstract: Glycerophospholipids are the principal fabric of cellular membranes. The pathways by which these lipids are synthesized were elucidated mainly through the work of Kennedy and colleagues in the late 1950s and early 1960s. Subsequently, attention turned to cell biological aspects of lipids: Where in the cell are lipids synthesized? How are lipids integrated into membranes to form a bilayer? How are they sorted and transported from their site of synthesis to other cellular destinations? These topics, collectively termed 'lipid topogenesis', were the subject of a review article in 1981 by Bell, Ballas and Coleman. We now assess what has been learned about early events of lipid topogenesis, i.e. "lipid synthesis, the integration of lipids into membranes, and lipid translocation across membranes", in the 35 years since the publication of this important review. We highlight the recent elucidation of the X-ray structures of key membrane enzymes of glycerophospholipid synthesis, progress on identifying lipid scramblase proteins needed to equilibrate lipids across membranes, and new complexities in the subcellular location and membrane topology of phosphatidylinositol synthesis revealed through a comparison of two unicellular model eukaryotes. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York 10065, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Chauhan
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
authors.forename: Luce
authors.initials: L
authors.lastname: Farine
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York 10065, USA.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Pandey
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York 10065, USA. Electronic address: akm2003@med.cornell.edu.
authors.forename: Anant K
authors.initials: AK
authors.lastname: Menon
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland. Electronic address: peter.buetikofer@ibmm.unibe.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Bütikofer
mesh_terms: D000818:Animals; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003567:Cytidine Diphosphate Diglycerides / Q000096:biosynthesis; D020404:Glycerophospholipids / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism
chemical_list: D003567:Cytidine Diphosphate Diglycerides; D020404:Glycerophospholipids; D008051:Lipid Bilayers; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
keywords: CDP-alcohol; Endoplasmic reticulum; Kennedy pathway; Membrane protein; Phospholipid; Scramblase