Catabolism of Bis(monoacylglycero)phosphate
The main subject studied in R. Zimmermann’s group is the functional characterization of lipolytic enzymes. Ongoing work is focused on the physiological role and regulation of acylglycerol and retinylester hydrolases, and on the development of specific inhibitors for ATGL. Within the next funding period we will start to investigate the metabolism of the lysosomal lipid bis(monoacylglycero)phosphate [BMP, also known as lysobisphosphatidic acid (LBPA)]. This lipid is found in inner membrane structures of lysosomes. It is resistant to acid hydrolases and forms a “platform” for lysosomal lipid-degrading enzymes. Therefore, BMP is considered as key activator for lysosomal lipid sorting and membrane digestion. Furthermore, BMP is a lipid marker for phospholipidosis and was identified as antigen for anti-phospholipid antibodies in patients suffering from anti-phospholipid syndrome. To date, very little is known about the synthesis and catabolism of this lipid. In a promising new project we identified a mammalian enzyme which degrades BMP with high specific activity. Further studies will focus on the role of this enzyme in lipid metabolism in vitro and in vivo.
Laboratory know-how and infrastructureThe Graz university cluster and the Institute of Molecular Biosciences (IMB) at the University of Graz is an internationally renowned center for lipid and energy metabolism research. State-of-the-art animal studies were made possible by the opening of the institute’s new animal facility under SPF conditions including a physiological unit (TSE Phenomaster). Therefore, the majority of our experimental work can be done at the IMB or in collaborating laboratories within the Graz network (lipidomics.uni-graz.at, lipotox.uni-graz.at). Special expertise is available in our group for gene cloning, protein expression, lipid and protein analysis, enzyme characterization, cell culture techniques, and generation and characterization of mutant mice.