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Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis

Despite the prominence of iron–sulfur cluster (ISC) proteins in bioenergetics, intermediary metabolism, and redox regulation of cellular, mitochondrial, and nuclear processes, these proteins have been given scarce attention in Drosophila. Moreover, biosynthesis and delivery of ISCs to target protein...

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Autores principales: Uhrigshardt, Helge, Rouault, Tracey A., Missirlis, Fanis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612401/
https://www.ncbi.nlm.nih.gov/pubmed/23444034
http://dx.doi.org/10.1007/s00775-013-0988-2
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author Uhrigshardt, Helge
Rouault, Tracey A.
Missirlis, Fanis
author_facet Uhrigshardt, Helge
Rouault, Tracey A.
Missirlis, Fanis
author_sort Uhrigshardt, Helge
collection PubMed
description Despite the prominence of iron–sulfur cluster (ISC) proteins in bioenergetics, intermediary metabolism, and redox regulation of cellular, mitochondrial, and nuclear processes, these proteins have been given scarce attention in Drosophila. Moreover, biosynthesis and delivery of ISCs to target proteins requires a highly regulated molecular network that spans different cellular compartments. The only Drosophila ISC biosynthetic protein studied to date is frataxin, in attempts to model Friedreich’s ataxia, a disease arising from reduced expression of the human frataxin homologue. One of several proteins involved in ISC biogenesis is heat shock protein cognate 20 (Hsc20). Here we characterize two piggyBac insertion mutants in Drosophila Hsc20 that display larval growth arrest and deficiencies in aconitase and succinate dehydrogenase activities, but not in isocitrate dehydrogenase activity; phenotypes also observed with ubiquitous frataxin RNA interference. Furthermore, a disruption of iron homeostasis in the mutant flies was evidenced by an apparent reduction in induction of intestinal ferritin with ferric iron accumulating in a subcellular pattern reminiscent of mitochondria. These phenotypes were specific to intestinal cell types that regulate ferritin expression, but were notably absent in the iron cells where ferritin is constitutively expressed and apparently translated independently of iron regulatory protein 1A. Hsc20 mutant flies represent an independent tool to disrupt ISC biogenesis in vivo without using the RNA interference machinery.
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spelling pubmed-36124012013-04-02 Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis Uhrigshardt, Helge Rouault, Tracey A. Missirlis, Fanis J Biol Inorg Chem Original Paper Despite the prominence of iron–sulfur cluster (ISC) proteins in bioenergetics, intermediary metabolism, and redox regulation of cellular, mitochondrial, and nuclear processes, these proteins have been given scarce attention in Drosophila. Moreover, biosynthesis and delivery of ISCs to target proteins requires a highly regulated molecular network that spans different cellular compartments. The only Drosophila ISC biosynthetic protein studied to date is frataxin, in attempts to model Friedreich’s ataxia, a disease arising from reduced expression of the human frataxin homologue. One of several proteins involved in ISC biogenesis is heat shock protein cognate 20 (Hsc20). Here we characterize two piggyBac insertion mutants in Drosophila Hsc20 that display larval growth arrest and deficiencies in aconitase and succinate dehydrogenase activities, but not in isocitrate dehydrogenase activity; phenotypes also observed with ubiquitous frataxin RNA interference. Furthermore, a disruption of iron homeostasis in the mutant flies was evidenced by an apparent reduction in induction of intestinal ferritin with ferric iron accumulating in a subcellular pattern reminiscent of mitochondria. These phenotypes were specific to intestinal cell types that regulate ferritin expression, but were notably absent in the iron cells where ferritin is constitutively expressed and apparently translated independently of iron regulatory protein 1A. Hsc20 mutant flies represent an independent tool to disrupt ISC biogenesis in vivo without using the RNA interference machinery. Springer-Verlag 2013-02-27 2013 /pmc/articles/PMC3612401/ /pubmed/23444034 http://dx.doi.org/10.1007/s00775-013-0988-2 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Paper
Uhrigshardt, Helge
Rouault, Tracey A.
Missirlis, Fanis
Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title_full Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title_fullStr Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title_full_unstemmed Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title_short Insertion mutants in Drosophila melanogaster Hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
title_sort insertion mutants in drosophila melanogaster hsc20 halt larval growth and lead to reduced iron–sulfur cluster enzyme activities and impaired iron homeostasis
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612401/
https://www.ncbi.nlm.nih.gov/pubmed/23444034
http://dx.doi.org/10.1007/s00775-013-0988-2
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