The role of lipids in exosome biology and intercellular communication: Function, analytics and applications

Abstract

Exosomes are extracellular vesicles that in recent years have received special attention for their regulatory functions in numerous biological processes. Recent evidence suggests a correlation between the composition of exosomes in body fluids and the progression of some disorders, such as cancer, diabetes and neurodegenerative diseases. In consequence, numerous studies have been performed to evaluate the composition of these vesicles, aiming to develop new biomarkers for diagnosis and to find novel therapeutic targets. On their part, lipids represent one of the most important components of exosomes, with important structural and regulatory functions during exosome biogenesis, release, targeting and cellular uptake. Therefore, exosome lipidomics has emerged as an innovative discipline for the discovery of novel lipid species with biomedical applications. This review summarizes the current knowledge about exosome lipids and their roles in exosome biology and intercellular communication. Furthermore, it presents the state-of-the-art analytical procedures used in exosome lipidomics while emphasizing how this emerging discipline is providing new insights for future applications of exosome lipids in biomedicine.

Keywords: exosome lipids; extracellular vesicles; lipid biomarkers; lipid trafficking; lipidomics.

FIGURE 1

The number of publications between 2000 and 2019 in PubMed related to exosome genomics, proteomics, or lipidomics. The search terms were “exosome” and “proteomic”, “proteomics” or “proteome” (green); “exosome” and “genomics”, “genomic” or “genome” (red); “exosome” and “lipidomics”, “lipidomic” or “lipidome” (blue)

FIGURE 2

Lipids in exosome biogenesis. Membrane domains enriched in cholesterol appear to provide adequate conditions for the recruitment of ESCRT machinery in MVBs. Ceramide and phosphatidic acid are cone‐shaped lipids that seem to induce spontaneous curvature of the MVBs membrane in an ESCRT‐independent manner. Ceramide is produced from sphingomyelin through the activity of the sphingomyelinases (SMase). On their part, phosphatidic acid is produced from phosphatidylcholine and diacylglycerol through the activity of the phospholipases (PLase) and diacylglycerol kinases (DGK), respectively. Furthermore, phosphatidic acid seems to interact with syndecan to enhance the recruitment of syntenin (Syn), ALIX and the ESCRT machinery

FIGURE 3

Relevant advantages and disadvantages of the most used analytical methods in lipidomic research. In LC‐MS and GC‐MS, analytes enter the MS detector as individual lipid species after chromatographic separation, overcoming some limitations observed in the direct infusion method. Despite the lower efficiency in lipid quantification observed in NMR spectroscopy, this method provides unique structural information about the lipid molecules

FIGURE 4

Summary of recent applications of exosomal lipids from different body fluids in biomedicine. The blue box shows the diseases in which exosomal lipids appear to be good candidates as diagnosis molecules classified by the source body fluid. The green box illustrates some disorders in which exosome lipids could act as therapeutic targets to control the disease progression. Aβ: amyloid‐β; PS: phosphatidylserine; DAGKα: diacylglycerol kinase α