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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...

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Detalles Bibliográficos
Autores principales: Palu, Rebecca A. S., Chow, Clement Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
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.
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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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