Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

Rabia, Maxence; Leuzy, Valentin; Soulage, Christophe O.; Durand, Annie; Fourmaux, Baptiste; Errazuriz-Cerda, Elisabeth; Köffel, René; Draeger, Annette; Colosetti, Pascal; Jalabert, Audrey; Filippo, Mathilde Di; Villard-Garon, Audrey; Bergerot, Cyrille; Luquain-Costaz, Céline; Moulin, Philippe; Rome, Sophie; Delton, Isabelle; Hullin-Matsuda, Françoise

doi:10.1016/j.biochi.2020.07.005

Cited by 28 publications

(21 citation statements)

References 80 publications

(123 reference statements)

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“…Importantly, EVs have bioactive lipids in their composition, such as ceramide, which may induce responses in recipient cells [183,184]. Thus, EVs lipidomics can contribute to understanding the biological mechanisms of EVs and identify potential biomarkers [151,185]. Mass spectrometry-based platforms and thin-layer chromatography (TLC) methods are used to study EVs lipidome profiling [186][187][188].…”

Section: Proteomic Transcriptome Lipidomic and Metabolomic Approachesmentioning

confidence: 99%

Extracellular Vesicles and Their Relationship with the Heart–Kidney Axis, Uremia and Peritoneal Dialysis

Azevedo

Cunha

Junho

et al. 2021

Toxins

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Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.

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Section: Proteomic Transcriptome Lipidomic and Metabolomic Approachesmentioning

confidence: 99%

Extracellular Vesicles and Their Relationship with the Heart–Kidney Axis, Uremia and Peritoneal Dialysis

Azevedo

Cunha

Junho

et al. 2021

Toxins

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“…(8) Virus factors can also hijack the extracellular vesicle EV secretory pathway to exit infected cells [ 63 ]. Recently, BMP (green conical cylinder) was considered as a new lipid signature of endosome-derived EVs characterized by the EV protein markers ESCRT protein TSG101, associated protein Alix, and the tetraspanins CD63 and CD81 [ 54 , 55 ]. The cholesterol transfer between NPC2 and membrane vesicles including between inner membranes of the LE/Lys compartment is favored by BMP [ 71 ].…”

Section: Bis(monoacylglycero)phosphate An Unusual Endolysosomal Phosmentioning

confidence: 99%

“…Thus, BMP is considered as a possible biomarker to follow disease progression [ 52 , 53 ]. We recently showed that BMP was increased in the urines of amiodarone-treated patients, a CAD antiarrhythmic drug, and was associated with extracellular vesicles (EVs) characterized as exosomes [ 54 ]. EVs form a heterogeneous group of membrane vesicles of variable sizes: “exosomes” of about 50–120 nm in diameter, originated from the ILVs after fusion of the multivesicular endosomes (MVEs) with the PM or “microvesicles” of about 50 nm to 1 μm in diameter, obtained from shedding of the PM [ 55 ].…”

Section: Bis(monoacylglycero)phosphate An Unusual Endolysosomal Phosmentioning

confidence: 99%

“…Presence of BMP in EVs seems to vary according to the cell type or the endolysosomal dysfunction. Due to its ubiquitous distribution in most mammalian cells and its selective localization in the endolysosome, we speculated that BMP could be a specific lipid signature of endosome-derived EVs in human urines [ 54 ]. However, this will require more analysis of EVs isolated from other extracellular biofluids.…”

Section: Bis(monoacylglycero)phosphate An Unusual Endolysosomal Phosmentioning

confidence: 99%

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Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

et al. 2020

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Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.

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“…In addition, lipids participate in EV biogenesis through various mechanisms, such as forming lipid rafts that concentrate or select cargo, altering membrane curvature, facilitating pitching from the multivesicular bodies, and participating in ESCRT-independent EV formation [30][31][32][33]. Furthermore, the lipids contained within EVs could be used as biomarkers for pathologies and/or to track their progression from their own respective biogenic pathway to the target cell(s) [34,35]. Specifically, EVs have been shown to contain bioactive lipids, such as ceramide (Cer) and diacylglyceride (DG) [27,36], which have been shown to be important for vesicular biogenesis, trafficking, and secretion [32,[37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Skeletal Muscle Cell Growth Alters the Lipid Composition of Extracellular Vesicles

et al. 2021

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We sought to characterize the lipid profile of skeletal muscle cell-derived Extracellular Vesicles (EVs) to determine if a hypertrophic stimulus would affect the lipid composition of C2C12 myotube-derived EVs. Analyses included C2C12 murine myoblasts differentiated into myotubes and treated with Insulin-Like Growth Factor 1 (IGF-1) for 24 h to induce hypertrophic growth. EVs were isolated from cell culture media, quantified using Nanoparticle Tracking Analysis (NTA) and analyzed using Transmission Electron Microscopy (TEM). EVs were homogenized and lipids extracted for quantification by Mass Spectrometry followed by downstream lipid class enrichment and lipid chain analysis. IGF-1 treatment elicited an increase in CD63 and CD81 levels (39% and 21%) compared to the controls (16%), respectively. Analysis revealed that skeletal muscle-derived EVs are enriched in bioactive lipids that are likely selectively incorporated into EVs during hypertrophic growth. IGF-1 treatment of myotubes had a significant impact on the levels of diacylglycerol (DG) and ceramide (Cer) in secreted EVs. Specifically, the proportion of unsaturated DG was two- to three-fold higher in EVs derived from IGF-treated cells, as compared to those from control cells. The levels of saturated DG were unaffected. Selective increases were similarly seen in C16- and C24-Cer but not in other species. Levels of free sphingoid bases tended to decrease, while those of sphingosine-1-phosphate was unaffected. Our results suggest that the lipid composition and biogenesis of skeletal muscle-derived EVs, are specific and highly selective during hypertrophic growth.

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Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

Cited by 28 publications

References 80 publications

Extracellular Vesicles and Their Relationship with the Heart–Kidney Axis, Uremia and Peritoneal Dialysis

Extracellular Vesicles and Their Relationship with the Heart–Kidney Axis, Uremia and Peritoneal Dialysis

Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

Skeletal Muscle Cell Growth Alters the Lipid Composition of Extracellular Vesicles

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