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

Rabia, Maxence; Leuzy, Valentin; Soulage, Christophe; Durand, Annie; Fourmaux, Baptiste; Errazuriz-Cerda, Elisabeth; Köffel, René; Draeger, Annette; Colosetti, Pascal; Jalabert, Audrey; Di Filippo, Mathilde; Villard-Garon, Audrey; Bergerot, Cyrille; Luquain-Costaz, Céline; Moulin, Philippe; Rome, Sophie; Delton, Isabelle; Hullin-Matsuda, Françoise (2020). Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles. Biochimie, 178, pp. 26-38. Elsevier Masson SAS 10.1016/j.biochi.2020.07.005

[img] Text
1-s2.0-S0300908420301590-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology

UniBE Contributor:

Köffel, René and Draeger, Annette

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0300-9084

Publisher:

Elsevier Masson SAS

Language:

English

Submitter:

René Köffel

Date Deposited:

25 Aug 2020 15:37

Last Modified:

26 Oct 2020 01:35

Publisher DOI:

10.1016/j.biochi.2020.07.005

PubMed ID:

32659447

Uncontrolled Keywords:

Bis(monoacylglycero)phosphate Docosahexaenoic acid Exosomes Extracellular vesicles Lysobisphosphatidic acid Lysosomal storage diseases

BORIS DOI:

10.7892/boris.146113

URI:

https://boris.unibe.ch/id/eprint/146113

Actions (login required)

Edit item Edit item
Provide Feedback