HDL holo-particle uptake maintains cellular cholesterol homeostasis

Cholesterol transport via high density lipoprotein (HDL) is an essential regulatory mechanism to remove excess cholesterol from peripheral tissue and to deliver it back to the liver for disposal. In contrast to the low density lipoprotein (LDL) receptor pathway, in which the entire LDL particle is degraded by the cell, HDL delivers only its core lipids to the cell, which is termed selective uptake.
In the present project we study holo-HDL particle uptake and resecretion as an alternative mechanism to maintain cholesterol homeostasis. This includes its physiological relevance as well as the receptors involved.

 

 How to examine lipid trafficking at high resolution


We are characterizing the uptake of HDL and its lipid (free and esterified cholesterol) in detail by CLEM (combined light-electron microscopy). Therefore, diaminobenzidine photooxidation is utilized to convert fluorescent protein labels and cholesterol probes into electron dense precipitates. This method allows the localization of proteins and lipids at nanometer resolution by transmission electron microscopy and electron tomography.

 

 

Lipoprotein modification alters cholesterol efflux capacity

Lipoproteins are modified in-vivo by inflammation, oxidative stress or altered renal function. We study the altered properties to exchange lipids between cells and lipoproteins and the molecular mechanism involved.