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Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response
Endoplasmic reticulum (ER) stress is an important modifier of human disease. Genetic variation in response genes is linked to inter-individual differences in the ER stress response. However, the mechanisms and pathways by which genetic modifiers are acting on the ER stress response remain unclear. I...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078684/ https://www.ncbi.nlm.nih.gov/pubmed/30081392 http://dx.doi.org/10.1371/journal.pgen.1007557 |
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author | Palu, Rebecca A. S. Chow, Clement Y. |
author_facet | Palu, Rebecca A. S. Chow, Clement Y. |
author_sort | Palu, Rebecca A. S. |
collection | PubMed |
description | Endoplasmic reticulum (ER) stress is an important modifier of human disease. Genetic variation in response genes is linked to inter-individual differences in the ER stress response. However, the mechanisms and pathways by which genetic modifiers are acting on the ER stress response remain unclear. In this study, we characterize the role of the long chain fatty acid elongase Baldspot (ELOVL6) in modifying the ER stress response and disease. We demonstrate that loss of Baldspot rescues degeneration and reduces IRE1 and PERK signaling and cell death in a Drosophila model of retinitis pigmentosa and ER stress (Rh1(G69D)). Dietary supplementation of stearate bypasses the need for Baldspot activity. Finally, we demonstrate that Baldspot regulates the ER stress response across different tissues and induction methods. Our findings suggest that ELOVL6 is a promising target in the treatment of not only retinitis pigmentosa, but a number of different ER stress-related disorders. |
format | Online Article Text |
id | pubmed-6078684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60786842018-08-28 Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response Palu, Rebecca A. S. Chow, Clement Y. PLoS Genet Research Article Endoplasmic reticulum (ER) stress is an important modifier of human disease. Genetic variation in response genes is linked to inter-individual differences in the ER stress response. However, the mechanisms and pathways by which genetic modifiers are acting on the ER stress response remain unclear. In this study, we characterize the role of the long chain fatty acid elongase Baldspot (ELOVL6) in modifying the ER stress response and disease. We demonstrate that loss of Baldspot rescues degeneration and reduces IRE1 and PERK signaling and cell death in a Drosophila model of retinitis pigmentosa and ER stress (Rh1(G69D)). Dietary supplementation of stearate bypasses the need for Baldspot activity. Finally, we demonstrate that Baldspot regulates the ER stress response across different tissues and induction methods. Our findings suggest that ELOVL6 is a promising target in the treatment of not only retinitis pigmentosa, but a number of different ER stress-related disorders. Public Library of Science 2018-08-06 /pmc/articles/PMC6078684/ /pubmed/30081392 http://dx.doi.org/10.1371/journal.pgen.1007557 Text en © 2018 Palu, Chow http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Palu, Rebecca A. S. Chow, Clement Y. Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title | Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title_full | Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title_fullStr | Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title_full_unstemmed | Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title_short | Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response |
title_sort | baldspot/elovl6 is a conserved modifier of disease and the er stress response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078684/ https://www.ncbi.nlm.nih.gov/pubmed/30081392 http://dx.doi.org/10.1371/journal.pgen.1007557 |
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