Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures
The enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in resp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258799/full |
| _version_ | 1797629509107712000 |
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| author | Andrea Schiffmann Lena Ahlswede Gerald Gimpl |
| author_facet | Andrea Schiffmann Lena Ahlswede Gerald Gimpl |
| author_sort | Andrea Schiffmann |
| collection | DOAJ |
| description | The enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in response to different ACAT inhibitors. The translocation was fast (within minutes), reversible and occurred in different cell types. Interestingly, oleic acid was able to fasten the re-translocation from vesicles back into the reticular ER network. The process of ACAT translocation could also be induced by cyclodextrins, cholesterol, lanosterol (but not 4-cholestene-3 one), 25-hydroxycholesterol, and by certain stress stimuli such as hyperosmolarity (sucrose treatment), temperature change, or high-density cultivation. In vitro esterification showed that ACAT remains fully active after it has been translocated to vesicles in response to hyperosmotic sucrose treatment of the cells. The translocation process was not accompanied by changes in the electrophoretic mobility of ACAT, even after chemical crosslinking. Interestingly, the protein synthesis inhibitor cycloheximide showed a stimulating effect on ACAT activity and prevented the translocation of ACAT from the ER into vesicles. |
| first_indexed | 2024-03-11T10:54:21Z |
| format | Article |
| id | doaj.art-a3702cc5f9c8488f8524ef4d3c47168d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-11T10:54:21Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-a3702cc5f9c8488f8524ef4d3c47168d2023-11-13T11:49:17ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.12587991258799Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structuresAndrea SchiffmannLena AhlswedeGerald GimplThe enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in response to different ACAT inhibitors. The translocation was fast (within minutes), reversible and occurred in different cell types. Interestingly, oleic acid was able to fasten the re-translocation from vesicles back into the reticular ER network. The process of ACAT translocation could also be induced by cyclodextrins, cholesterol, lanosterol (but not 4-cholestene-3 one), 25-hydroxycholesterol, and by certain stress stimuli such as hyperosmolarity (sucrose treatment), temperature change, or high-density cultivation. In vitro esterification showed that ACAT remains fully active after it has been translocated to vesicles in response to hyperosmotic sucrose treatment of the cells. The translocation process was not accompanied by changes in the electrophoretic mobility of ACAT, even after chemical crosslinking. Interestingly, the protein synthesis inhibitor cycloheximide showed a stimulating effect on ACAT activity and prevented the translocation of ACAT from the ER into vesicles.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258799/fullacyl-CoA:cholesterol acyltransferase (ACAT)bovine serum albumin (BSA)cycloheximide (CHX)disuccinimidyl suberate (DSS)cholesterol ester (CE)dansyl-cholestanol (DChol) |
| spellingShingle | Andrea Schiffmann Lena Ahlswede Gerald Gimpl Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures Frontiers in Molecular Biosciences acyl-CoA:cholesterol acyltransferase (ACAT) bovine serum albumin (BSA) cycloheximide (CHX) disuccinimidyl suberate (DSS) cholesterol ester (CE) dansyl-cholestanol (DChol) |
| title | Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures |
| title_full | Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures |
| title_fullStr | Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures |
| title_full_unstemmed | Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures |
| title_short | Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures |
| title_sort | reversible translocation of acyl coa cholesterol acyltransferase acat between the endoplasmic reticulum and vesicular structures |
| topic | acyl-CoA:cholesterol acyltransferase (ACAT) bovine serum albumin (BSA) cycloheximide (CHX) disuccinimidyl suberate (DSS) cholesterol ester (CE) dansyl-cholestanol (DChol) |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258799/full |
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