Late Endosomal Membranes Rich in Lysobisphosphatidic Acid Regulate Cholesterol Transport

Nat Cell Biol. 1999 Jun;1(2):113-8. doi: 10.1038/10084.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiphospholipid Syndrome / genetics
  • Antiphospholipid Syndrome / metabolism
  • Cell Line
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Cricetinae
  • Endocytosis
  • Endosomes / drug effects
  • Endosomes / genetics
  • Endosomes / metabolism*
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • Humans
  • Intracellular Membranes / metabolism*
  • Lysophospholipids / metabolism*
  • Lysosomes / metabolism
  • Membrane Lipids / metabolism*
  • Monoglycerides
  • Niemann-Pick Diseases / genetics
  • Niemann-Pick Diseases / metabolism*
  • Niemann-Pick Diseases / pathology
  • Receptor, IGF Type 2 / metabolism
  • Recombinant Proteins / metabolism
  • Skin / metabolism*
  • Skin / pathology
  • Skin / ultrastructure
  • Zinc / pharmacology

Substances

  • Lysophospholipids
  • Membrane Lipids
  • Monoglycerides
  • Receptor, IGF Type 2
  • Recombinant Proteins
  • bis(monoacylglyceryl)phosphate
  • Cholesterol
  • Zinc