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      Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology

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          Abstract

          Exosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in cholesterol, SM, glycosphingolipids, and phosphatidylserine. Lipids not only have a structural role in exosomal membranes but also are essential players in exosome formation and release to the extracellular environment. Our knowledge about the importance of lipids in exosome biology is increasing due to recent technological developments in lipidomics and a stronger focus on the biological functions of these molecules. Here, we review the available information about the lipid composition of exosomes. Special attention is given to ether lipids, a relatively unexplored type of lipids involved in membrane trafficking and abundant in some exosomes. Moreover, we discuss how the lipid composition of exosome preparations may provide useful information about their purity. Finally, we discuss the role of phosphoinositides, membrane phospholipids that help to regulate membrane dynamics, in exosome release and how this process may be linked to secretory autophagy. Knowledge about exosome lipid composition is important to understand the biology of these vesicles and to investigate possible medical applications.

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          Most cited references102

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          Shedding light on the cell biology of extracellular vesicles

          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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            Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

            In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
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              Is Open Access

              Biological properties of extracellular vesicles and their physiological functions

              In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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                Author and article information

                Journal
                J Lipid Res
                J. Lipid Res
                jlr
                jlr
                jlr
                Journal of Lipid Research
                The American Society for Biochemistry and Molecular Biology
                0022-2275
                1539-7262
                January 2019
                3 August 2018
                3 August 2018
                : 60
                : 1
                : 9-18
                Affiliations
                Department of Molecular Cell Biology, [* ] Institute for Cancer Research, Oslo University Hospital-Norwegian Radium Hospital , 0379 Oslo, Norway
                Department of Biosciences, [] University of Oslo , 0316 Oslo, Norway
                Author notes
                [1 ]To whom correspondence should be addressed. e-mail: Alicia.Martinez.Llorente@ 123456rr-research.no
                Article
                r084343
                10.1194/jlr.R084343
                6314266
                30076207
                2efdc30a-3025-4c6b-a120-b3c470ff11fc
                Copyright © 2019 Skotland et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.

                Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license.

                History
                : 13 February 2018
                : 24 July 2018
                Funding
                Funded by: Norwegian Cancer Society, open-funder-registry 10.13039/100008730;
                Funded by: Norwegian Research Council, open-funder-registry 10.13039/501100005416;
                Funded by: Southern and Eastern Norway Regional Health Authority, open-funder-registry 10.13039/501100006095;
                Categories
                Thematic Review Series
                Thematic Review Series: Exosomes and Microvesicles: Lipids as Key Components of their Biogenesis and Functions

                Biochemistry
                cellular membranes,extracellular vesicles,lipidomics,vesicular transport.
                Biochemistry
                cellular membranes, extracellular vesicles, lipidomics, vesicular transport.

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