Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes
The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/64690 |
| _version_ | 1818019903534268416 |
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| author | Xinyu Zhu Aren Boulet Katherine M Buckley Casey B Phillips Micah G Gammon Laura E Oldfather Stanley A Moore Scot C Leary Paul A Cobine |
| author_facet | Xinyu Zhu Aren Boulet Katherine M Buckley Casey B Phillips Micah G Gammon Laura E Oldfather Stanley A Moore Scot C Leary Paul A Cobine |
| author_sort | Xinyu Zhu |
| collection | DOAJ |
| description | The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins. |
| first_indexed | 2024-04-14T07:58:55Z |
| format | Article |
| id | doaj.art-d7782b206ce2471e920d657626b83899 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:58:55Z |
| publishDate | 2021-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d7782b206ce2471e920d657626b838992022-12-22T02:04:58ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.64690Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotesXinyu Zhu0https://orcid.org/0000-0002-7618-1501Aren Boulet1Katherine M Buckley2https://orcid.org/0000-0002-6585-8943Casey B Phillips3Micah G Gammon4Laura E Oldfather5Stanley A Moore6Scot C Leary7https://orcid.org/0000-0001-8488-7822Paul A Cobine8https://orcid.org/0000-0001-6012-0985Department of Biological Sciences, Auburn University, Auburn, United StatesDepartment of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, CanadaDepartment of Biological Sciences, Auburn University, Auburn, United StatesDepartment of Biological Sciences, Auburn University, Auburn, United StatesDepartment of Biological Sciences, Auburn University, Auburn, United StatesDepartment of Biological Sciences, Auburn University, Auburn, United StatesDepartment of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, CanadaDepartment of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, CanadaDepartment of Biological Sciences, Auburn University, Auburn, United StatesThe mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins.https://elifesciences.org/articles/64690mitochondrial carrier familycopperphosphategene duplicationsevolutionmitochondria |
| spellingShingle | Xinyu Zhu Aren Boulet Katherine M Buckley Casey B Phillips Micah G Gammon Laura E Oldfather Stanley A Moore Scot C Leary Paul A Cobine Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes eLife mitochondrial carrier family copper phosphate gene duplications evolution mitochondria |
| title | Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| title_full | Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| title_fullStr | Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| title_full_unstemmed | Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| title_short | Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| title_sort | mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes |
| topic | mitochondrial carrier family copper phosphate gene duplications evolution mitochondria |
| url | https://elifesciences.org/articles/64690 |
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