CTP:phosphocholine cytidylyltransferase (CCT) is the ratelimiting enzyme of phosphatidylcholine biosynthesis. CCT is localized to the surfaces of lipid droplets during their expansion. (A) Choline biosynthesis pathway. (B) drosophila S2 cells cultured with oleic acid. CK, choline kinase. CPT, CDPcholine: diacylglycerol cholinephosphotransferase. Bar, 1 μm.
Because energy availability varies, living organisms need to store energy. This is done most efficiently as triacylglycerols (TGs). Within cells, TGs and other nonpolar lipids are stored in cytosolic lipid droplets (LDs). Excessive accumulation of lipids in LDs within tissues underlies the pathogenesis of diseases, such as obesity, diabetes, fatty liver and atherosclerosis. Additionally, lipid storage in LDs is a focus of efforts to increase oil yields from crops or microorganisms. An understanding of how cells synthesize, store and utilize lipids is, therefore, of fundamental importance.
We study the mechanisms of cellular lipid synthesis and storage. Our studies range from the basic biology of diacylglycerol acyltransferases (DGATs) and other enzymes involved in TG synthesis to genetic models aimed at discovering genes that govern LD formation. Our model systems include yeast, mammalian cells, mice and human induced pluripotent stem (iPS) cells. Our discoveries of basic mechanisms from in vitro and cellular studies are tested in whole organisms for their applications to physiology and disease.