ApoE4 upregulates the activity of mitochondria‐associated ER membranes
In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria‐associated endoplasmic reticulum (ER...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718413/ https://www.ncbi.nlm.nih.gov/pubmed/26564908 http://dx.doi.org/10.15252/embr.201540614 |
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author | Tambini, Marc D Pera, Marta Kanter, Ellen Yang, Hua Guardia‐Laguarta, Cristina Holtzman, David Sulzer, David Area‐Gomez, Estela Schon, Eric A |
author_facet | Tambini, Marc D Pera, Marta Kanter, Ellen Yang, Hua Guardia‐Laguarta, Cristina Holtzman, David Sulzer, David Area‐Gomez, Estela Schon, Eric A |
author_sort | Tambini, Marc D |
collection | PubMed |
description | In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria‐associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin‐deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the ε4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte‐conditioned media (ACM) model, we now show that ER–mitochondrial communication and MAM function—as measured by the synthesis of phospholipids and of cholesteryl esters, respectively—are increased significantly in cells treated with ApoE4‐containing ACM as compared to those treated with ApoE3‐containing ACM. Notably, this effect was seen with lipoprotein‐enriched preparations, but not with lipid‐free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease. |
format | Online Article Text |
id | pubmed-4718413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47184132016-02-11 ApoE4 upregulates the activity of mitochondria‐associated ER membranes Tambini, Marc D Pera, Marta Kanter, Ellen Yang, Hua Guardia‐Laguarta, Cristina Holtzman, David Sulzer, David Area‐Gomez, Estela Schon, Eric A EMBO Rep Scientific Reports In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria‐associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin‐deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the ε4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte‐conditioned media (ACM) model, we now show that ER–mitochondrial communication and MAM function—as measured by the synthesis of phospholipids and of cholesteryl esters, respectively—are increased significantly in cells treated with ApoE4‐containing ACM as compared to those treated with ApoE3‐containing ACM. Notably, this effect was seen with lipoprotein‐enriched preparations, but not with lipid‐free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease. John Wiley and Sons Inc. 2015-11-12 2016-01 /pmc/articles/PMC4718413/ /pubmed/26564908 http://dx.doi.org/10.15252/embr.201540614 Text en © 2015 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Scientific Reports Tambini, Marc D Pera, Marta Kanter, Ellen Yang, Hua Guardia‐Laguarta, Cristina Holtzman, David Sulzer, David Area‐Gomez, Estela Schon, Eric A ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title | ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title_full | ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title_fullStr | ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title_full_unstemmed | ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title_short | ApoE4 upregulates the activity of mitochondria‐associated ER membranes |
title_sort | apoe4 upregulates the activity of mitochondria‐associated er membranes |
topic | Scientific Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718413/ https://www.ncbi.nlm.nih.gov/pubmed/26564908 http://dx.doi.org/10.15252/embr.201540614 |
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