WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins

Dye, Danielle E.; Bieniawski, Mark A.; Wright, Sarah Christine Elisabeth; McCauley, Angela; Coombe, Deirdre R.; Mousley, Carl J.

doi:10.1194/jlr.r088682

Cited by 1 publication

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References 73 publications

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“…Oxysterols are associated with a large variety of cellular effectors linked to atherosclerosis. Among them, oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a family of lipid binding/transfer proteins conserved in eukaryotes [7][8][9]. Several reports have addressed the role of ORPs in intracellular cholesterol trafficking and homeostasis, for example: control of endoplasmic reticulum-late endosomes (ER -LE) contacts and LE motility (ORP1L), neutral lipid metabolism (ORP2), cholesterol egress from LE (ORP5), macrophage lipid and high-density lipoprotein metabolism (ORP8), apolipoprotein B-100 secretion (ORP10), and adipogenesis (ORP11) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Bis(monoacylglycero)phosphate regulates oxysterol binding protein-related protein 11 dependent sterol trafficking

Arnal-Levron

Chen

Greimel

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Bis(Monoacylglycero) Phosphate (BMP) is a unique phospholipid localized in late endosomes, a critical cellular compartment in low density lipoprotein (LDL)-cholesterol metabolism. In previous work, we demonstrated the important role of BMP in the regulation of macrophage cholesterol homeostasis. BMP exerts a protective role against the pro-apoptotic effect of oxidized LDL (oxLDL) by reducing the production of deleterious oxysterols. As the intracellular sterol traffic in macrophages is in part regulated by oxysterol binding protein (OSBP) and OSBPrelated proteins (ORPs), we investigated the role of ORP11, localized at the Golgi-late endosomes interface, in the BMP-mediated protection from oxLDL/oxysterol cytotoxicity. Stably silencing of ORP11 in mouse RAW264.7 macrophages via a shRNA lentiviruses system had no effect on BMP production. However, ORP11 knockdown abrogated the protective action of BMP against oxLDL induced apoptosis. In oxLDL treated control cells, BMP enrichment was associated with reduced generation of 7-oxysterols, while these oxysterol species were abundant in the ORP11 knock-down cells. Of note, BMP enrichment in ORP11 knock-down cells was associated with a drastic increase in free cholesterol and linked to a decrease of cholesterol efflux. The expression of ATP-binding cassette-transporter G1 (ABCG1) was also reduced in the ORP11 knock-down cells. These observations demonstrate a cooperative function of OPR11 and BMP, in intracellular cholesterol trafficking in cultured macrophages. We suggest that BMP favors the egress of cholesterol from late endosomes via an ORP11-dependent mechanism, resulting in a reduced production of cytotoxic 7-oxysterols.

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