Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport

T Kobayashi, MH Beuchat, M Lindsay, S Frias… - Nature cell …, 1999 - nature.com
T Kobayashi, MH Beuchat, M Lindsay, S Frias, RD Palmiter, H Sakuraba, RG Parton
Nature cell biology, 1999nature.com
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 …
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.
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