BBB Seminar: Elina Ikonen
Cholesterol-regulated signaling and transport in endo-lysosomes
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Institute of Biomedicine, University of Helsinki, Finland
Cholesterol is taken up by cells through receptor mediated endocytosis of low-density lipoprotein (LDL) particles. While LDL receptors recycle to the plasma membrane (PM), LDL cholesteryl esters are hydrolyzed in the acidic endocytic compartments by acid lipase. The Niemann-Pick type C2 and C1 proteins (NPC1, NPC2) co-operate in capturing the hydrolyzed cholesterol, apparently for delivery to the lysosomal limiting membrane. How cholesterol then leaves lysosomes and what signals activate the following transfer processes is less clear. An increase in the endosomal cholesterol content, such as in the absence of NPC1 or NPC2 function, reduces endosome motility and results in an endo-lysosomal lipid traffic jam. I will discuss our recent studies to identify protein machineries that control the transfer of LDL cholesterol between endosomal compartments and the removal of cholesterol from endo-lysosomes to the PM.
Host: Jaakko Saraste, Department of Biomedicine