| First Author | Chen W | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 47 | Pages | 43564-9 |
| PubMed ID | 11559713 | Mgi Jnum | J:72766 |
| Mgi Id | MGI:2153573 | Doi | 10.1074/jbc.M107938200 |
| Citation | Chen W, et al. (2001) Preferential ATP-binding Cassette Transporter A1-mediated Cholesterol Efflux from Late Endosomes/Lysosomes. J Biol Chem 276(47):43564-9 |
| abstractText | Recently, ATP-binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, has been shown to stimulate phospholipid and cholesterol efflux to apolipoprotein A-I (apoA-I); however, little is known concerning the cellular cholesterol pools that act as the source of cholesterol for ABCA1-mediated efflux. We observed a higher level of isotopic and mass cholesterol efflux from mouse peritoneal macrophages labeled with [(3)H]cholesterol/acetyl low density lipoprotein (where cholesterol accumulates in late endosomes and lysosomes) compared with cells labeled with [(3)H]cholesterol with 10% fetal bovine serum, suggesting that late endosomes/lysosomes act as a preferential source of cholesterol for ABCA1-mediated efflux. Consistent with this idea, macrophages from Niemann-Pick C1 mice that have an inability to exit cholesterol from late endosomes/lysosomes showed a profound defect in cholesterol efflux to apoA-I. In contrast, phospholipid efflux to apoA-I was normal in Niemann-Pick C1 macrophages, as was cholesterol efflux following plasma membrane cholesterol labeling. These results suggest that cholesterol deposited in late endosomes/lysosomes preferentially acts as a source of cholesterol for ABCA1-mediated cholesterol efflux. |
