Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Klugherz, Isabel, Basch, Marion, Ng, Natanya, Zhu, Zhaojun, Wagener, Nikola, Wagener, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785140338485100544
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
work_keys_str_mv AT klugherzisabel onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth
AT baschmarion onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth
AT ngnatanya onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth
AT zhuzhaojun onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth
AT wagenernikola onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth
AT wagenerjohannes onlyoneofthreebcs1homologsinaspergillusfumigatusconfersrespiratorygrowth