Abstract
The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann-Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of the lysosomal enzyme receptor is impaired. Our results show that the characteristic network of lysobisphosphatidic acid-rich membranes contained within multivesicular late endosomes regulates cholesterol transport, presumably by acting as a collection and distribution device. The results also suggest that similar endosomal defects accompany the anti-phospholipid syndrome and NPC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiphospholipid Syndrome / genetics
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Antiphospholipid Syndrome / metabolism
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Cell Line
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Cells, Cultured
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Cholesterol / metabolism*
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Cricetinae
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Endocytosis
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Endosomes / drug effects
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Endosomes / genetics
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Endosomes / metabolism*
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Fibroblasts / metabolism
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Fibroblasts / ultrastructure
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Humans
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Intracellular Membranes / metabolism*
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Lysophospholipids / metabolism*
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Lysosomes / metabolism
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Membrane Lipids / metabolism*
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Monoglycerides
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Niemann-Pick Diseases / genetics
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Niemann-Pick Diseases / metabolism*
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Niemann-Pick Diseases / pathology
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Receptor, IGF Type 2 / metabolism
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Recombinant Proteins / metabolism
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Skin / metabolism*
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Skin / pathology
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Skin / ultrastructure
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Zinc / pharmacology
Substances
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Lysophospholipids
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Membrane Lipids
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Monoglycerides
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Receptor, IGF Type 2
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Recombinant Proteins
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bis(monoacylglyceryl)phosphate
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Cholesterol
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Zinc