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Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth
The mitochondrial translocase Bcs1 is required for the correct assembly of complex III of the mitochondrial respiratory chain. Because of its importance, Bcs1 was recently proposed as a target for antifungal agents. The function of this AAA (ATPase Associated with diverse cellular Activities) protei...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672213/ https://www.ncbi.nlm.nih.gov/pubmed/37998879 http://dx.doi.org/10.3390/jof9111074 |
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author | Klugherz, Isabel Basch, Marion Ng, Natanya Zhu, Zhaojun Wagener, Nikola Wagener, Johannes |
author_facet | Klugherz, Isabel Basch, Marion Ng, Natanya Zhu, Zhaojun Wagener, Nikola Wagener, Johannes |
author_sort | Klugherz, Isabel |
collection | PubMed |
description | The mitochondrial translocase Bcs1 is required for the correct assembly of complex III of the mitochondrial respiratory chain. Because of its importance, Bcs1 was recently proposed as a target for antifungal agents. The function of this AAA (ATPase Associated with diverse cellular Activities) protein has been extensively characterized in Saccharomyces cerevisiae. This yeast as well as previously studied mammals each encode only one homolog. In contrast, the pathogenic mold Aspergillus fumigatus encodes three putative Bcs1 homologs, none of which have been characterized to date. To study the role of these three homologs in A. fumigatus, conditional and deletion mutants of the respective genes AFUA_3G13000 (bcs1A), AFUA_4G01260 (bcs1B), and AFUA_2G14760 (bcs1C) were generated. A deletion or downregulation of bcs1A resulted in drastically reduced growth and sporulation rates and in a significantly altered susceptibility to azole antifungals. In contrast, mutants lacking Bcs1B or Bcs1C did not show any phenotypes differing from the wild type. Salicylhydroxamic acid—an inhibitor of the alternative oxidase that allows the respiratory chain to bypass complex III in some species—caused a complete growth arrest of the bcs1A deletion mutant. In a Galleria mellonella infection model, the deletion of bcs1A resulted in significantly decreased virulence. Only Bcs1A was able to partially complement a deletion of BCS1 in S. cerevisiae. The subcellular localization of Bcs1B and Bcs1C outside of mitochondria suggests that these Bcs1 homologs exert cellular functions different from that of Bcs1. Our data demonstrate that Bcs1A is the sole Bcs1 ortholog in A. fumigatus. |
format | Online Article Text |
id | pubmed-10672213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106722132023-11-02 Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth Klugherz, Isabel Basch, Marion Ng, Natanya Zhu, Zhaojun Wagener, Nikola Wagener, Johannes J Fungi (Basel) Article The mitochondrial translocase Bcs1 is required for the correct assembly of complex III of the mitochondrial respiratory chain. Because of its importance, Bcs1 was recently proposed as a target for antifungal agents. The function of this AAA (ATPase Associated with diverse cellular Activities) protein has been extensively characterized in Saccharomyces cerevisiae. This yeast as well as previously studied mammals each encode only one homolog. In contrast, the pathogenic mold Aspergillus fumigatus encodes three putative Bcs1 homologs, none of which have been characterized to date. To study the role of these three homologs in A. fumigatus, conditional and deletion mutants of the respective genes AFUA_3G13000 (bcs1A), AFUA_4G01260 (bcs1B), and AFUA_2G14760 (bcs1C) were generated. A deletion or downregulation of bcs1A resulted in drastically reduced growth and sporulation rates and in a significantly altered susceptibility to azole antifungals. In contrast, mutants lacking Bcs1B or Bcs1C did not show any phenotypes differing from the wild type. Salicylhydroxamic acid—an inhibitor of the alternative oxidase that allows the respiratory chain to bypass complex III in some species—caused a complete growth arrest of the bcs1A deletion mutant. In a Galleria mellonella infection model, the deletion of bcs1A resulted in significantly decreased virulence. Only Bcs1A was able to partially complement a deletion of BCS1 in S. cerevisiae. The subcellular localization of Bcs1B and Bcs1C outside of mitochondria suggests that these Bcs1 homologs exert cellular functions different from that of Bcs1. Our data demonstrate that Bcs1A is the sole Bcs1 ortholog in A. fumigatus. MDPI 2023-11-02 /pmc/articles/PMC10672213/ /pubmed/37998879 http://dx.doi.org/10.3390/jof9111074 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Klugherz, Isabel Basch, Marion Ng, Natanya Zhu, Zhaojun Wagener, Nikola Wagener, Johannes Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title | Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title_full | Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title_fullStr | Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title_full_unstemmed | Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title_short | Only One of Three Bcs1 Homologs in Aspergillus fumigatus Confers Respiratory Growth |
title_sort | only one of three bcs1 homologs in aspergillus fumigatus confers respiratory growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672213/ https://www.ncbi.nlm.nih.gov/pubmed/37998879 http://dx.doi.org/10.3390/jof9111074 |
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