Team : Metabolism and trafficking of cholesterol and oxidized derivatives in macrophages, Inserm UMR1060, CarMeN, INSA Lyon, Villeurbanne, France

Key members : Isabelle Delton (PU), Céline Luquain-Costaz (MCU), Françoise Hullin-Matsuda (CR Inserm)

Contacts: Isabelle Delton, isabelle.delton@insa-lyon.fr

 

Research activities: Our main goal is to elucidate the mechanisms of intracellular cholesterol trafficking, in particular at the level of the late endosomal compartment which plays a crucial role in LDL derived-cholesterol sorting and export outside the macrophage. We have emphasized the involvement of a specific endosomal phospholipid, bis(monoacylglycerol)phosphate (BMP) in controlling the intracellular distribution of cholesterol issued from endocytosed LDL, thereby regulating several cholesterol homeostasis genes and cholesterol efflux. We also found that BMP regulates oxysterol production in macrophages. Current works are investigating the cooperation of BMP with actors of non-vesicular transport (i.e., proteins including ORPs) or vesicular transport (i.e. exosomes) of cholesterol and oxysterols.

We attempt to identify mechanisms /therapeutic targets that will have significant implications for new strategy development to better control cholesterol and oxysterol metabolism that is dysregulated in atherosclerosis.

 

Key papers related to ENOR

 

In vitro oxidized HDL and HDL from type 2 diabetes patients have reduced ability to efflux oxysterols from THP-1 macrophages. Chen Y, Arnal-Levron M, Hullin-Matsuda F, Knibbe C, Moulin P, Luquain-Costaz C, Delton I. Biochimie 2018, https://doi.org/10.1016/j.biochi.2018.04.018

 

THP-1 macrophages oxidized cholesterol generating 7-derivative oxysterols specifically released by HDL. Chen Y, Arnal-Levron M, Lagarde M, Moulin P, Luquain-Costaz C, Delton I. Steroids 2015, 99:212-218

 

Bis(monoacylglycero)phosphate reduces oxysterol formation and apoptosis in macrophages exposed to oxidized LDL. Arnal-Levron M, Chen Y, Delton-Vandenbroucke I, Luquain-Costaz C. Biochem Pharmacol. 2013, 86(1):115-21

 

Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-Binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux. Luquain-Costaz C, Lefai E, Arnal-Levron M, Markina D, Sakaï S, Euthine V, Makino A, Guichardant M, Yamashita S, Kobayashi T, Lagarde M, Moulin P, Delton-Vandenbroucke I. Arterioscler Thromb Vasc Biol. 2013, 33(8):1803-11

 

Bis(monoacylglycero)phosphate, a peculiar phospholipid to control the fate of cholesterol : implications in pathology. Hullin-Matsuda F., Luquain-Costaz C., Bouvier J. and Delton-Vandenbroucke I. Prostaglandins. Leukot. Essent. Fatty Acids, 2009, 81:313-324. Revue

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