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Open Access 01-12-2016 | Research

Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts

Authors: Urszula Liwak-Muir, Hapsatou Mamady, Turaya Naas, Quinlan Wylie, Skye McBride, Matthew Lines, Jean Michaud, Stephen D. Baird, Pranesh K. Chakraborty, Martin Holcik

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

Abstract

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.

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Title: Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts
Authors: Urszula Liwak-Muir
Hapsatou Mamady
Turaya Naas
Quinlan Wylie
Skye McBride
Matthew Lines
Jean Michaud
Stephen D. Baird
Pranesh K. Chakraborty
Martin Holcik
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-016-0466-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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