BMP is a glycerophospholipid found in intraluminal vesicles of late endosomes/lysosomes and at low concentrations in the circulation. BMP plays a key role in cellular lipid degradation pathways by stimulating the activity of acidic lipid hydrolases and lipid-binding/transfer proteins. BMP concentrations in tissues and serum increase strobgly in genetic and drug-induced lysosomal storage disorders. Despite its central role in lipid sorting and its association with lysosomal dysfunction, little is known about the nutritional regulation of BMP and the enzymes catalyzing BMP synthesis and degradation. PP07 elucidates the molecular pathways regulating tissue and serum BMP levels in health and disease to uncover metabolic relationships essential for understanding lipid degradation and sorting in acidic organelles. Specifically, this project identifies and characterizes enzymes catalyzing BMP synthesis in mammalian cells, examines whether human subjects with metabolic disorders exhibit aberrant BMP metabolism, and characterizes the role of the BMP-hydrolyzing enzyme ABHD6 in BMP metabolism in vivo.
