title: Exogenous ether lipids predominantly target mitochondria.
abstract: Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking.
authors.affiliation: Life and Medical Sciences Institute, LIMES, University of Bonn, Bonn, Germany. lars.kuerschner@uni-bonn.de
authors.forename: Lars
authors.initials: L
authors.lastname: Kuerschner
authors.forename: Doris
authors.initials: D
authors.lastname: Richter
authors.forename: Hans Kristian
authors.initials: HK
authors.lastname: Hannibal-Bach
authors.forename: Anne
authors.initials: A
authors.lastname: Gaebler
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Christer S
authors.initials: CS
authors.lastname: Ejsing
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiele
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000737:chemistry; D005995:Glyceryl Ethers; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010742:Phospholipid Ethers / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005995:Glyceryl Ethers; D010742:Phospholipid Ethers; C026659:edelfosine