Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol
The abundance of cell cholesterol is governed by multiple regulatory proteins in the endoplasmic reticulum (ER) which, in turn, are under the control of the cholesterol in that organelle. But how does ER cholesterol reflect cell (mostly plasma membrane) cholesterol? We have systematically quantitate...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1999-12-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520321015 |
| _version_ | 1818739573714321408 |
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| author | Yvonne Lange Jin Ye Mike Rigney Theodore L. Steck |
| author_facet | Yvonne Lange Jin Ye Mike Rigney Theodore L. Steck |
| author_sort | Yvonne Lange |
| collection | DOAJ |
| description | The abundance of cell cholesterol is governed by multiple regulatory proteins in the endoplasmic reticulum (ER) which, in turn, are under the control of the cholesterol in that organelle. But how does ER cholesterol reflect cell (mostly plasma membrane) cholesterol? We have systematically quantitated this relationship for the first time. We found that ER cholesterol in resting human fibroblasts comprised ∼0.5% of the cell total. The ER pool rose by more than 10-fold in less than 1 h as cell cholesterol was increased by ∼50% from below to above its physiological value. The curve describing the dependence of ER on plasma membrane cholesterol had a J shape. Its vertex was at the ambient level of cell cholesterol and thus could correspond to a threshold. A variety of class 2 amphiphiles (e.g., U18666A) rapidly reduced ER cholesterol but caused only minor alterations in the J-curve. In contrast, brief exposure of cells to the oxysterol, 25-hydroxycholesterol, elevated and linearized the J-curve, increasing ER cholesterol at all values of cell cholesterol. This finding can explain the rapid action of oxysterols on cholesterol homeostasis. Other functions have also been observed to depend acutely on the level of plasma membrane cholesterol near its physiological level, perhaps reflecting a cholesterol-dependent structural or organizational transition in the bilayer. Such a physical transition could serve as a set-point above which excess plasma membrane cholesterol is transported to the ER where it would signal regulatory proteins to down-regulate its further accumulation.—Lange, Y., J. Ye, M. Rigney, and T. L. Steck. Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol. |
| first_indexed | 2024-12-18T01:26:59Z |
| format | Article |
| id | doaj.art-03de1f20e7364d8b89f164bc7d416f38 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:26:59Z |
| publishDate | 1999-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-03de1f20e7364d8b89f164bc7d416f382022-12-21T21:25:41ZengElsevierJournal of Lipid Research0022-22751999-12-01401222642270Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterolYvonne Lange0Jin Ye1Mike Rigney2Theodore L. Steck3To whom correspondence should be addressed.; Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612Department of Biochemistry and Molecular Biology, University of Chicago, 920 E. 58th Street, Chicago, IL 60637The abundance of cell cholesterol is governed by multiple regulatory proteins in the endoplasmic reticulum (ER) which, in turn, are under the control of the cholesterol in that organelle. But how does ER cholesterol reflect cell (mostly plasma membrane) cholesterol? We have systematically quantitated this relationship for the first time. We found that ER cholesterol in resting human fibroblasts comprised ∼0.5% of the cell total. The ER pool rose by more than 10-fold in less than 1 h as cell cholesterol was increased by ∼50% from below to above its physiological value. The curve describing the dependence of ER on plasma membrane cholesterol had a J shape. Its vertex was at the ambient level of cell cholesterol and thus could correspond to a threshold. A variety of class 2 amphiphiles (e.g., U18666A) rapidly reduced ER cholesterol but caused only minor alterations in the J-curve. In contrast, brief exposure of cells to the oxysterol, 25-hydroxycholesterol, elevated and linearized the J-curve, increasing ER cholesterol at all values of cell cholesterol. This finding can explain the rapid action of oxysterols on cholesterol homeostasis. Other functions have also been observed to depend acutely on the level of plasma membrane cholesterol near its physiological level, perhaps reflecting a cholesterol-dependent structural or organizational transition in the bilayer. Such a physical transition could serve as a set-point above which excess plasma membrane cholesterol is transported to the ER where it would signal regulatory proteins to down-regulate its further accumulation.—Lange, Y., J. Ye, M. Rigney, and T. L. Steck. Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol.http://www.sciencedirect.com/science/article/pii/S0022227520321015homeostasissensor25-hydroxycholesterolU18666A |
| spellingShingle | Yvonne Lange Jin Ye Mike Rigney Theodore L. Steck Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol Journal of Lipid Research homeostasis sensor 25-hydroxycholesterol U18666A |
| title | Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| title_full | Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| title_fullStr | Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| title_full_unstemmed | Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| title_short | Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| title_sort | regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol |
| topic | homeostasis sensor 25-hydroxycholesterol U18666A |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520321015 |
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