Sunday September 23, 2012 16:00 - 16:30 @ Rhodes 8 

Mechanisms of lipoprotein-derived lipid transfer in mammalian cells

Abstract:

Background: A major mechanism of lipid entry into mammalian cells is via receptor-mediated endocytosis of low-density lipoprotein (LDL)-particles. While LDL-receptors recycle to the plasma membrane for further cargo uptake the LDL-derived lipids are hydrolyzed in the acidic compartments. Cholesteryl esters are broken down into free cholesterol and a fatty acid, and sphingolipids yield ceramide as their common degradation product that can be further broken down into sphingosine and a fatty acid. 

Observations: We aim to understand how these released cholesterol and sphingolipid degradation products are removed from the endo-lysosomal membranes and transferred to other subcellular membranes, and how the transfer of cholesterol and sphingolipids may be coupled. We have identified proteins involved in these processes by incorporating fluorescently or radioactively labeled cholesterol or sphingolipids into LDL particles and feeding them into cells in which selected cytosolic or lysosomal membrane proteins have been acutely depleted using siRNAs. In addition, we have manipulated the endosomal pathway using pharmacological treatments. 

Conclusions: While cholesterol and sphingolipids often co-sequester in late endosomal compartments different mechanisms of transfer operate in the endo-lysosomal exit of cholesterol and sphingolipid degradation products. Examples of specific protein mediated transfer mechanisms will be highlighted.