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Endocytosis of lipoproteins

  • Paolo Zanoni
    Affiliations
    Institute for Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland

    Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Srividya Velagapudi
    Affiliations
    Institute for Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland

    Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Mustafa Yalcinkaya
    Affiliations
    Institute for Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland

    Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Lucia Rohrer
    Affiliations
    Institute for Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland

    Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Arnold von Eckardstein
    Correspondence
    Corresponding author. University Hospital Zurich, Institute of Clinical Chemistry, Raemistrasse 100, CH 8091, Zurich, Switzerland.
    Affiliations
    Institute for Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland

    Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    Search for articles by this author

      Highlights

      • Receptor mediated endocytosis is essential for the regulation of metabolism and function of all lipoprotein classes.
      • The hepatic LDL-receptor is a determinant of LDL-cholesterol plasma levels and target of several anti-atherosclerotic drugs.
      • Receptors mediating the endocytosis of HDL or lipoprotein(a) are still a matter of controversy or even new discovery.
      • The uptake of lipoproteins into non-degrading intracellular compartments is little understood.
      • These itineraries may be essential for re-secretion, storage, or execution of intracellular functions of lipoproteins.

      Abstract

      During their metabolism, all lipoproteins undergo endocytosis, either to be degraded intracellularly, for example in hepatocytes or macrophages, or to be re-secreted, for example in the course of transcytosis by endothelial cells. Moreover, there are several examples of internalized lipoproteins sequestered intracellularly, possibly to exert intracellular functions, for example the cytolysis of trypanosoma. Endocytosis and the subsequent intracellular itinerary of lipoproteins hence are key areas for understanding the regulation of plasma lipid levels as well as the biological functions of lipoproteins. Indeed, the identification of the low-density lipoprotein (LDL)-receptor and the unraveling of its transcriptional regulation led to the elucidation of familial hypercholesterolemia as well as to the development of statins, the most successful therapeutics for lowering of cholesterol levels and risk of atherosclerotic cardiovascular diseases. Novel limiting factors of intracellular trafficking of LDL and the LDL receptor continue to be discovered and to provide drug targets such as PCSK9. Surprisingly, the receptors mediating endocytosis of high-density lipoproteins or lipoprotein(a) are still a matter of controversy or even new discovery. Finally, the receptors and mechanisms, which mediate the uptake of lipoproteins into non-degrading intracellular itineraries for re-secretion (transcytosis, retroendocytosis), storage, or execution of intracellular functions, are largely unknown.

      Keywords

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