Acyl-CoA-independent acylglycerol synthesis

Disorders of lipid metabolism are a major health risk factor leading to life and health threatening diseases, such as type 2 diabetes and metabolic syndrome. The detailed understanding of the molecular pathways underlying metabolic disorders can provide novel strategies for their treatment. The biosynthesis of di- and triacylglycerol (DAG and TAG) represents a central metabolic pathway affecting lipid and energy homeostasis. Mammalian cells synthesize DAG and TAG in reactions using acyl-CoA as acyl donor and monoacylglycerol (MAG) and DAG as acceptor, respectively. Plants, yeast, and bacteria developed an additional mechanism of acylglycerol synthesis using phospholipids as acyl donors and MAG or DAG as acceptor. In plants, these transacylase reactions crucially affect the flux of carbon into the TAG stores of seeds, while the contribution of acyl-CoA independent acylglycerol synthesis in mammalian cells remains elusive. The central objective of this project is to characterize acyl-CoA-independent acyltransferases in mammalian cells. We believe that our observations can provide important new insights into the mechanisms and regulation of lipid synthesis in mammalian cells.