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Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts
BACKGROUND: SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912790/ https://www.ncbi.nlm.nih.gov/pubmed/27317422 http://dx.doi.org/10.1186/s13023-016-0466-3 |
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author | Liwak-Muir, Urszula Mamady, Hapsatou Naas, Turaya Wylie, Quinlan McBride, Skye Lines, Matthew Michaud, Jean Baird, Stephen D. Chakraborty, Pranesh K. Holcik, Martin |
author_facet | Liwak-Muir, Urszula Mamady, Hapsatou Naas, Turaya Wylie, Quinlan McBride, Skye Lines, Matthew Michaud, Jean Baird, Stephen D. Chakraborty, Pranesh K. Holcik, Martin |
author_sort | Liwak-Muir, Urszula |
collection | PubMed |
description | BACKGROUND: SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known. RESULTS: We show that the disease causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Analysis of cellular respiration and oxidative phosphorylation (OXPHOS) complexes demonstrates that both basal and maximal respiration rates are decreased in patient cells, which may be attributed to an observed decrease in the abundance of select proteins of the OXPHOS complexes. CONCLUSIONS: Our data provides further insight into cellular pathophysiology of SIFD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-016-0466-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4912790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49127902016-06-19 Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts Liwak-Muir, Urszula Mamady, Hapsatou Naas, Turaya Wylie, Quinlan McBride, Skye Lines, Matthew Michaud, Jean Baird, Stephen D. Chakraborty, Pranesh K. Holcik, Martin Orphanet J Rare Dis Research BACKGROUND: SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known. RESULTS: We show that the disease causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Analysis of cellular respiration and oxidative phosphorylation (OXPHOS) complexes demonstrates that both basal and maximal respiration rates are decreased in patient cells, which may be attributed to an observed decrease in the abundance of select proteins of the OXPHOS complexes. CONCLUSIONS: Our data provides further insight into cellular pathophysiology of SIFD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-016-0466-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-18 /pmc/articles/PMC4912790/ /pubmed/27317422 http://dx.doi.org/10.1186/s13023-016-0466-3 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Liwak-Muir, Urszula Mamady, Hapsatou Naas, Turaya Wylie, Quinlan McBride, Skye Lines, Matthew Michaud, Jean Baird, Stephen D. Chakraborty, Pranesh K. Holcik, Martin Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title | Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title_full | Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title_fullStr | Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title_full_unstemmed | Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title_short | Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts |
title_sort | impaired activity of cca-adding enzyme trnt1 impacts oxphos complexes and cellular respiration in sifd patient-derived fibroblasts |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912790/ https://www.ncbi.nlm.nih.gov/pubmed/27317422 http://dx.doi.org/10.1186/s13023-016-0466-3 |
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