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The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation

Members of the bacterial and mitochondrial iron–sulfur cluster (ISC) assembly machinery include the so-called A-type ISC proteins, which support the assembly of a subset of Fe/S apoproteins. The human genome encodes two A-type proteins, termed ISCA1 and ISCA2, which are related to Saccharomyces cere...

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Autores principales: Sheftel, Alex D., Wilbrecht, Claudia, Stehling, Oliver, Niggemeyer, Brigitte, Elsässer, Hans-Peter, Mühlenhoff, Ulrich, Lill, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315811/
https://www.ncbi.nlm.nih.gov/pubmed/22323289
http://dx.doi.org/10.1091/mbc.E11-09-0772
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author Sheftel, Alex D.
Wilbrecht, Claudia
Stehling, Oliver
Niggemeyer, Brigitte
Elsässer, Hans-Peter
Mühlenhoff, Ulrich
Lill, Roland
author_facet Sheftel, Alex D.
Wilbrecht, Claudia
Stehling, Oliver
Niggemeyer, Brigitte
Elsässer, Hans-Peter
Mühlenhoff, Ulrich
Lill, Roland
author_sort Sheftel, Alex D.
collection PubMed
description Members of the bacterial and mitochondrial iron–sulfur cluster (ISC) assembly machinery include the so-called A-type ISC proteins, which support the assembly of a subset of Fe/S apoproteins. The human genome encodes two A-type proteins, termed ISCA1 and ISCA2, which are related to Saccharomyces cerevisiae Isa1 and Isa2, respectively. An additional protein, Iba57, physically interacts with Isa1 and Isa2 in yeast. To test the cellular role of human ISCA1, ISCA2, and IBA57, HeLa cells were depleted for any of these proteins by RNA interference technology. Depleted cells contained massively swollen and enlarged mitochondria that were virtually devoid of cristae membranes, demonstrating the importance of these proteins for mitochondrial biogenesis. The activities of mitochondrial [4Fe-4S] proteins, including aconitase, respiratory complex I, and lipoic acid synthase, were diminished following depletion of the three proteins. In contrast, the mitochondrial [2Fe-2S] enzyme ferrochelatase and cellular heme content were unaffected. We further provide evidence against a localization and direct Fe/S protein maturation function of ISCA1 and ISCA2 in the cytosol. Taken together, our data suggest that ISCA1, ISCA2, and IBA57 are specifically involved in the maturation of mitochondrial [4Fe-4S] proteins functioning late in the ISC assembly pathway.
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spelling pubmed-33158112012-06-16 The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation Sheftel, Alex D. Wilbrecht, Claudia Stehling, Oliver Niggemeyer, Brigitte Elsässer, Hans-Peter Mühlenhoff, Ulrich Lill, Roland Mol Biol Cell Articles Members of the bacterial and mitochondrial iron–sulfur cluster (ISC) assembly machinery include the so-called A-type ISC proteins, which support the assembly of a subset of Fe/S apoproteins. The human genome encodes two A-type proteins, termed ISCA1 and ISCA2, which are related to Saccharomyces cerevisiae Isa1 and Isa2, respectively. An additional protein, Iba57, physically interacts with Isa1 and Isa2 in yeast. To test the cellular role of human ISCA1, ISCA2, and IBA57, HeLa cells were depleted for any of these proteins by RNA interference technology. Depleted cells contained massively swollen and enlarged mitochondria that were virtually devoid of cristae membranes, demonstrating the importance of these proteins for mitochondrial biogenesis. The activities of mitochondrial [4Fe-4S] proteins, including aconitase, respiratory complex I, and lipoic acid synthase, were diminished following depletion of the three proteins. In contrast, the mitochondrial [2Fe-2S] enzyme ferrochelatase and cellular heme content were unaffected. We further provide evidence against a localization and direct Fe/S protein maturation function of ISCA1 and ISCA2 in the cytosol. Taken together, our data suggest that ISCA1, ISCA2, and IBA57 are specifically involved in the maturation of mitochondrial [4Fe-4S] proteins functioning late in the ISC assembly pathway. The American Society for Cell Biology 2012-04-01 /pmc/articles/PMC3315811/ /pubmed/22323289 http://dx.doi.org/10.1091/mbc.E11-09-0772 Text en © 2012 Sheftel et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Sheftel, Alex D.
Wilbrecht, Claudia
Stehling, Oliver
Niggemeyer, Brigitte
Elsässer, Hans-Peter
Mühlenhoff, Ulrich
Lill, Roland
The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title_full The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title_fullStr The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title_full_unstemmed The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title_short The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation
title_sort human mitochondrial isca1, isca2, and iba57 proteins are required for [4fe-4s] protein maturation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315811/
https://www.ncbi.nlm.nih.gov/pubmed/22323289
http://dx.doi.org/10.1091/mbc.E11-09-0772
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