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

Rabia M; Leuzy V; Soulage C; Durand A; Fourmaux B; Errazuriz-Cerda E; Köffel R; Draeger A; Colosetti P; Jalabert A; Di Filippo M; Villard-Garon A; Bergerot C; Luquain-Costaz C; Moulin P; Rome S; Delton I; Hullin-Matsuda F

doi:10.1016/j.biochi.2020.07.005

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Journal article

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

Rabia M Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Leuzy V Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Soulage C Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Durand A Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Fourmaux B Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France; Functional Lipidomics Platform, CarMeN Laboratory / IMBL-INSA Lyon, 69621, Villeurbanne Cedex, France.
Errazuriz-Cerda E Univ-Lyon, CIQLE (Centre D'Imagerie Quantitative Lyon Est) Rockefeller, Lyon, France.
Köffel R Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
Draeger A Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
Colosetti P Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Jalabert A Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Di Filippo M Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France; Department of Biochemistry and Molecular Biology, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, France.
Villard-Garon A Department of Endocrinology, Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon, Lyon, Bron, France.
Bergerot C Department of Cardiology, Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon, Lyon, Bron, France.
Luquain-Costaz C Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Moulin P Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France; Department of Endocrinology, Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon, Lyon, Bron, France.
Rome S Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Delton I Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France.
Hullin-Matsuda F Univ-Lyon, CarMeN Laboratory, Inserm U1060, INRAe U1397, INSA Lyon, Villeurbanne, France. Electronic address: francoise.hullin-matsuda@inserm.fr.

2020-07-14

Published in:

Biochimie. - 2020

English 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.

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