Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes
- Auburn University, United States
- University of Saskatchewan, Canada
- University Saskatchewan, Canada
Abstract
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 modelling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated a 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.
Data availability
All data generated or analyzed during this study are included in the manuscript, supplemental file, and available on GenBank.
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Author details
Funding
National Institutes of Health (R01GM120211)
- Scot C Leary
- Paul A Cobine
National Science Foundation (EF 2021886)
- Katherine M Buckley
Alabama Agricultural Experiment Station
- Paul A Cobine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Zhu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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