Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies

doi:10.1016/j.biochi.2006.10.014

Biochimie

Volume 89, Issue 2, February 2007, Pages 205-212

https://doi.org/10.1016/j.biochi.2006.10.014 Get rights and content

Abstract

Exosomes are part of the family of “bioactive vesicles” and appear to be involved in distal communications between cells. They vehiculate bioactive lipids and lipolytic enzymes and their biogenesis require specific lipids and a membrane reorganisation. Their biogenesis pathway could be a way to secrete enzymes involved in lipid signalling and to generate “particulate agonists”. However, this pathway seems also to be used by pathogens such as HIV. This review will consider several aspects of lipidomics studies which might help to understand the fate and role of these fascinating vesicles.

Introduction

Bioactive vesicles are receiving increasing interest since they are an important process to enhance life diversity. Exosomes are the only type of bioactive vesicles originating from an intracellular compartment, namely MultiVesicular Bodies (MVB, or Late Endosomes) and released out of the cell. Several reviews describing “the exosome pathway” are now available [1], [2]. First observed in 1987 during reticulocyte maturation [3] and extensively investigated in that field [4], the interest towards these vesicles was triggered again 10 years later, when it was observed they were enriched in MHC II and released out of B lymphocytes following cell activation [5]. The strong potency of exosomes loaded with a specific antigen to eradicate tumors in mice was demonstrated two years later [6]. Phase I clinical trials were completed a year ago in humans, and exosomes appear as a promising tool for autologous treatments in cancer [7].

In that context exosome lipidomics appears as a requirement for the elaboration of “reconstituted exosomes”, with the purpose of elaborating a tool in cancer treatment independent of any biological source. Vehiculating therapeutic drugs by encapsulation inside a liposome has been the dream of lipidologists for decades and many attempts are currently undergoing [8]. In all cases, lipid composition of liposomes has been empirical, based on the knowledge acquired for years on lipid organisation in membranes and subsequent physicochemical properties. Instead, exosomes offer the first opportunity of a “therapeutic vesicle” whose lipid composition and organisation could be a starting point to devise efficient liposomes, vehiculating tumor antigens to boost the immune response towards tumors.

During these last years, lipidomics has appeared as an emerging field, since genomics and proteomics could not bring all the responses scientists were expecting in the perspective to cure a panel of pathologies [9]. The lack of powerful tools to analyse the complexity of lipids has been overcome by novel analytical approaches, including liquid chromatography coupled to powerful mass spectrometry equipments [10] easier to use than in the past, allowing for example the elaboration of “lipid arrays” [11]. This review will summarize the present knowledge on exosome lipidomics, in order to better understand how to regulate their biogenesis which undoubtly requires appropriated lipid mediators.

Section snippets

Analytical lipidomics

This part will consider the lipid composition and membrane organisation of exosomes.

Cellular lipidomics

This part of the review will consider the cellular origin of lipids recovered in exosome composition.

Functional lipidomics

This part will consider the dynamics of lipids involved in exosome biogenesis and the role of some lipolytic enzymes on their biological functions.

However, exosome-bound LPC might act efficiently in target cells such as dendritic cells (DC). Exosomes appear to be endocytosed by immature dendritic cells and to enhance both cell maturation and antigen presentation [38]. Mature DC cells will then release new exosomes more efficient than those originating from immature cells [39]. It has been shown

Conclusion

Exosomes are a new type of bioactive vesicles which are suspected to play a key role in many biological responses in the body [53]. On model membranes, LBPA (BMP) seems to be essential for their biogenesis, but this requires confirmation in cells. In any cases, a better understanding on the metabolism of this lipid is necessary. Differences in exosomes lipid composition and membrane organisation have appeared between reticulocyte and immunocompetent cell-derived exosomes. Lipid composition of

Acknowledgements

This work is funded by the “Ligue Nationale Contre le Cancer (Comités Tarn et Garonne et Ariège)” and the “Agence Nationale de Recherche sur le Sida (ANRS)”. C. Subra is supported by the ANRS.

Part of the experimental work used for this review was presented at the First Workshop on “Exosomes: Biological Significance”, Montreal, Canada, May 20–21 (2005); at the First ANRS Research Forum “1er Forum de Recherches Fondamentales et cliniques sur le VIH: du patient au laboratoire”, Paris, April 6–7

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Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies

Abstract

Introduction

Section snippets

Analytical lipidomics

Cellular lipidomics

Functional lipidomics

Conclusion

Acknowledgements

Curr. Opin. Cell Biol.

J. Biol. Chem.

Blood Cells Mol. Dis.

Blood

Biochim. Biophys. Acta

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J. Exp. Med.