Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> 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...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/11/1074 |
| _version_ | 1797458731278008320 |
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| author | Isabel Klugherz Marion Basch Natanya Ng Zhaojun Zhu Nikola Wagener Johannes Wagener |
| author_facet | Isabel Klugherz Marion Basch Natanya Ng Zhaojun Zhu Nikola Wagener Johannes Wagener |
| author_sort | Isabel Klugherz |
| collection | DOAJ |
| 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 <i>Saccharomyces cerevisiae</i>. This yeast as well as previously studied mammals each encode only one homolog. In contrast, the pathogenic mold <i>Aspergillus fumigatus</i> encodes three putative Bcs1 homologs, none of which have been characterized to date. To study the role of these three homologs in <i>A. fumigatus</i>, conditional and deletion mutants of the respective genes AFUA_3G13000 (<i>bcs1A</i>), AFUA_4G01260 (<i>bcs1B</i>), and AFUA_2G14760 (<i>bcs1C</i>) were generated. A deletion or downregulation of <i>bcs1A</i> 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 <i>bcs1A</i> deletion mutant. In a <i>Galleria mellonella</i> infection model, the deletion of <i>bcs1A</i> resulted in significantly decreased virulence. Only Bcs1A was able to partially complement a deletion of <i>BCS1</i> in <i>S. cerevisiae</i>. 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 <i>A. fumigatus</i>. |
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| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T16:42:21Z |
| publishDate | 2023-11-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-ac291a05da22499fafd6505c2ace48612023-11-24T14:51:02ZengMDPI AGJournal of Fungi2309-608X2023-11-01911107410.3390/jof9111074Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory GrowthIsabel Klugherz0Marion Basch1Natanya Ng2Zhaojun Zhu3Nikola Wagener4Johannes Wagener5Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Medizinische Fakultät, Ludwig-Maximilians-Universität München, 80336 Munich, GermanyZell- und Entwicklungsbiologie, Department Biologie II, Ludwig-Maximilians-Universität München, Planegg-Martinsried, 82152 Munich, GermanyDepartment of Clinical Microbiology, School of Medicine, Trinity College Dublin, The University of Dublin, St James’s Hospital Campus, D08 RX0X Dublin, IrelandMax von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Medizinische Fakultät, Ludwig-Maximilians-Universität München, 80336 Munich, GermanyZell- und Entwicklungsbiologie, Department Biologie II, Ludwig-Maximilians-Universität München, Planegg-Martinsried, 82152 Munich, GermanyMax von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Medizinische Fakultät, Ludwig-Maximilians-Universität München, 80336 Munich, GermanyThe 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 <i>Saccharomyces cerevisiae</i>. This yeast as well as previously studied mammals each encode only one homolog. In contrast, the pathogenic mold <i>Aspergillus fumigatus</i> encodes three putative Bcs1 homologs, none of which have been characterized to date. To study the role of these three homologs in <i>A. fumigatus</i>, conditional and deletion mutants of the respective genes AFUA_3G13000 (<i>bcs1A</i>), AFUA_4G01260 (<i>bcs1B</i>), and AFUA_2G14760 (<i>bcs1C</i>) were generated. A deletion or downregulation of <i>bcs1A</i> 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 <i>bcs1A</i> deletion mutant. In a <i>Galleria mellonella</i> infection model, the deletion of <i>bcs1A</i> resulted in significantly decreased virulence. Only Bcs1A was able to partially complement a deletion of <i>BCS1</i> in <i>S. cerevisiae</i>. 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 <i>A. fumigatus</i>.https://www.mdpi.com/2309-608X/9/11/1074Bcs1mitochondriacomplex IIIazoles<i>Aspergillus fumigatus</i> |
| spellingShingle | Isabel Klugherz Marion Basch Natanya Ng Zhaojun Zhu Nikola Wagener Johannes Wagener Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth Journal of Fungi Bcs1 mitochondria complex III azoles <i>Aspergillus fumigatus</i> |
| title | Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth |
| title_full | Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth |
| title_fullStr | Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth |
| title_full_unstemmed | Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth |
| title_short | Only One of Three Bcs1 Homologs in <i>Aspergillus fumigatus</i> Confers Respiratory Growth |
| title_sort | only one of three bcs1 homologs in i aspergillus fumigatus i confers respiratory growth |
| topic | Bcs1 mitochondria complex III azoles <i>Aspergillus fumigatus</i> |
| url | https://www.mdpi.com/2309-608X/9/11/1074 |
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