Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes

eLife

Scot C Leary¹  Stanley A Moore¹  Aren Boulet¹  Paul A Cobine²  Katherine M Buckley²  Laura E Oldfather²  Xinyu Zhu²  Casey B Phillips²  Micah G Gammon² 

[1] Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada;Department of Biological Sciences, Auburn University, Auburn, United States;

关键词: mitochondrial carrier family;    copper;    phosphate;    gene duplications;    evolution;    mitochondria;   

DOI  :  10.7554/eLife.64690

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown