Bis(monoacylglycero)phosphate: an endolysosomal phospholipid with antioxidant and antiatherogenic properties

Bis(monoacylglycero)phosphate (BMP) is a unique anionic glycerophospholipid almost exclusively localized to late endosomes/lysosomes (LE/LY), where it accounts for up to 70 % of the total phospholipid content of intraluminal vesicle membranes. It displays distinctive structural features, including an unusual sn-1:sn-1' stereochemistry and enrichment in long-chain unsaturated fatty acids such as oleic acid and docosahexaenoic acid (DHA). These properties underlie its roles in vesicular trafficking, lysosomal hydrolase activation, and cholesterol transport. Beyond these functions, BMP may act as an adaptive stress mediator in macrophages exposed to atherogenic lipoproteins. Its enrichment in DHA and localization within the oxidatively vulnerable LE/LY compartment suggest a role in limiting oxidative damage. Consistently, BMP has been associated with reduced formation of cholesterol oxidation products (oxysterols) and reactive oxygen species, as well as preservation of mitochondrial function and autophagic flux. However, a central unresolved issue concerns its dose-dependent effect on cholesterol homeostasis. This review synthesizes current knowledge on BMP biology and proposes a conceptual framework in which BMP functions as a stress response hub in lipid-laden macrophages.