Bis (monoacylglycero) phosphate interfacial properties and lipolysis by pancreatic lipase-related protein 2, an enzyme present in THP-1 human monocytes
“…ABHD6 hydrolyzes BMP with high specific activity, but it is clearly not the only enzyme capable of catalyzing this reaction. Published work suggests that a member of the carboxylesterase family ( 45 ), pancreatic lipase related protein 2 (PLRP2) ( 46 ), and ABHD12 ( 47 ) can degrade BMP in vitro . PLRP2 is found in the pancreatic juice but might also possess intracellular functions.…”
Background: Bis(monoacylglycero)phosphate (BMP) plays a key role in the degradation and sorting of lipids in acidic organelles.Results: ABHD6 degrades BMP and co-localizes with late endosomes/lysosomes. Knockdown of ABHD6 increases hepatic BMP levels.Conclusion: ABHD6 controls BMP catabolism.Significance: ABHD6 is part of the late endosomal/lysosomal lipid-sorting machinery.
“…ABHD6 hydrolyzes BMP with high specific activity, but it is clearly not the only enzyme capable of catalyzing this reaction. Published work suggests that a member of the carboxylesterase family ( 45 ), pancreatic lipase related protein 2 (PLRP2) ( 46 ), and ABHD12 ( 47 ) can degrade BMP in vitro . PLRP2 is found in the pancreatic juice but might also possess intracellular functions.…”
Background: Bis(monoacylglycero)phosphate (BMP) plays a key role in the degradation and sorting of lipids in acidic organelles.Results: ABHD6 degrades BMP and co-localizes with late endosomes/lysosomes. Knockdown of ABHD6 increases hepatic BMP levels.Conclusion: ABHD6 controls BMP catabolism.Significance: ABHD6 is part of the late endosomal/lysosomal lipid-sorting machinery.
“…So far, however, no BMP flippase has been identified [87]. Based on monomolecular film experiments with individual phospholipids and a mixture of PC, PE and PI ± BMP, we proposed another hypothesis based on the pH-dependent surface occupancy of phospholipids in the presence of BMP [88]. Indeed, at a surface pressure of 30 mN/m corresponding to the lateral pressure in natural membranes [89], the presence of BMP induces a decrease in the mean molecular area of phospholipids at pH 5.5 compared to pH 8 ( Fig.…”
Section: Bmp and Vesicular/endosomal Traffickingmentioning
confidence: 96%
“…Adapted from Ref. [88], in which experimental details are provided. NB: It is worth noting that these experiments were performed with the a, a 0 -BMP isomer that differs from the intracellular b, b 0 -BMP isomer used for demonstrating vesicular budding in lisosomes [86].…”
Section: Dual Behaviour Of Bmp In Viral Infection and Antiviral Effectsmentioning
The anti-malarial drug Chloroquine (CQ) and its derivative hydroxychloroquine have shown antiviral activities in vitro against many viruses, including coronaviruses, dengue virus and the biosafety level 4 Nipah and Hendra paramyxoviruses. The in vivo efficacy of CQ in the treatment of COVID-19 is currently a matter of debate. CQ is a lysosomotrophic compound that accumulates in lysosomes, as well as in food vacuoles of Plasmodium falciparum. In the treatment of malaria, CQ impairs the digestion and growth of the parasite by increasing the pH of the food vacuole. Similarly, it is assumed that the antiviral effects of CQ results from the increase of lysosome pH and the inhibition of acidic proteases involved in the maturation of virus fusion protein. CQ has however other effects, among which phospholipidosis, characterized by the accumulation of multivesicular bodies within the cell. The increase in phospholipid species particularly concerns bis(monoacylglycero)phosphate (BMP), a specific lipid of late endosomes involved in vesicular trafficking and pH-dependent vesicle budding. It was shown previously that drugs like progesterone, the cationic amphiphile U18666A and the phospholipase inhibitor methyl arachidonyl fluoro phosphonate (MAFP) induce the accumulation of BMP in THP-1 cells and decrease cell infection by human immunodeficiency virus. HIV viral particles were found to be retained into large endosomal-type vesicles, preventing virus spreading. Since BMP was also reported to favour virus entry through hijacking of the endocytic pathway, we propose here that BMP could play a dual role in viral infection, with its antiviral effects triggered by lysosomotropic drugs like CQ.
“…However, acyl chain turnover was demonstrated comparable to other phospholipids [ 41 ]. Phospholipase activities able to metabolize BMP have been described depending on the acidic environment and substrate presentation [ 42 , 43 ], including a pancreatic-lipase related protein 2 (PLRP2) also found in lysosome [ 44 , 45 ] and recently the monoacylglycerol hydrolase α/β hydrolase domain-containing 6 ABHD6 [ 46 , 47 ]. Fig.…”
Section: Bis(monoacylglycero)phosphate An Unusual Endolysosomal Phosmentioning
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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