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- Title
Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts.
- Authors
Liwak-Muir, Urszula; Mamady, Hapsatou; Naas, Turaya; Wylie, Quinlan; McBride, Skye; Lines, Matthew; Michaud, Jean; Baird, Stephen D.; Chakraborty, Pranesh K.; Holcik, Martin
- Abstract
<bold>Background: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Our data provides further insight into cellular pathophysiology of SIFD.
- Subjects
DEVELOPMENTAL delay; FIBROBLASTS; OXIDATIVE phosphorylation; PATHOLOGICAL physiology; CELLULAR pathology; ANEMIA; BIOLOGICAL transport; CELL culture; CELL physiology; COMPARATIVE studies; ELECTRON microscopy; ENERGY metabolism; FLUORESCENT antibody technique; RESEARCH methodology; MEDICAL cooperation; MITOCHONDRIA; GENETIC mutation; RESEARCH; WESTERN immunoblotting; EVALUATION research; NUCLEOTIDYLTRANSFERASES
- Publication
Orphanet Journal of Rare Diseases, 2016, Vol 11, p1
- ISSN
1750-1172
- Publication type
journal article
- DOI
10.1186/s13023-016-0466-3