Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport.
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.
Kobayashi
T
T
Department of Biochemistry, University of Geneva, Switzerland.
Beuchat
M H
MH
Lindsay
M
M
Frias
S
S
Palmiter
R D
RD
Sakuraba
H
H
Parton
R G
RG
Gruenberg
J
J
D000818:Animals; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D004705:Endocytosis; D011992:Endosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D050178:Monoglycerides; D009542:Niemann-Pick Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015032:Zinc / Q000494:pharmacology
D008246:Lysophospholipids; D008563:Membrane Lipids; D050178:Monoglycerides; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; C012786:bis(monoacylglyceryl)phosphate; D002784:Cholesterol; D015032:Zinc