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

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.

Keywords: cellular membranes; extracellular vesicles; lipidomics; vesicular transport..

Fig. 1.

Exosome release. MVBs, also called late endosomes, can fuse with lysosomes, with autophagosomes to form amphistomes, and with the plasma membrane. After fusion of MVBs with the plasma membrane the ILVs of MVBs are released as EVs and then called exosomes.

Fig. 2.

Enrichment of lipid classes in PC-3 cells and PC-3 exosomes. GM1, GM2, GM3, and GD1 are different negatively charged glycosphingolipids. This figure is reprinted from (36) with permission from Elsevier. DAG, diacylglycerol; Gb3, globotriaosylceramide; LacCer, lactosylceramide; LPE, lysophosphatidylethanolamine; LPI, lysophosphatidylinositol; PA, phosphatidic acid; PG, phosphatidylglycerol.