title: Expression of the yeast cation diffusion facilitators Mmt1 and Mmt2 affects mitochondrial and cellular iron homeostasis: evidence for mitochondrial iron export.
abstract: Mmt1 and Mmt2 are highly homologous yeast members of the cation diffusion facilitator transporter family localized to mitochondria. Overexpression of MMT1/2 led to changes in cellular metal homeostasis (increased iron sensitivity, decreased cobalt sensitivity, increased sensitivity to copper), oxidant generation, and increased sensitivity to H2O2. The phenotypes due to overexpression of MMT1&2 were similar to that seen in cells with deletions in MRS3 and MRS4, genes that encode the mitochondrial iron importers. Overexpression of MMT1&2 resulted in induction of the low iron transcriptional response, similar to that seen in Δmrs3Δmr4 cells. This low iron transcriptional response was suppressed by deletion of CCC1, the gene that encodes the vacuolar iron importer. Measurement of the activity of the iron-dependent gentisate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans expressed in yeast cytosol, showed that changes in Mmt1/2 levels affected cytosol iron concentration even in the absence of Ccc1. Overexpression of MMT1 resulted in increased cytosolic iron whereas deletion of MMT1/MMT2 led to decreased cytosolic iron. These results support the hypothesis that Mmt1/2 function as mitochondrial iron exporters.
authors.affiliation: From the Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Liangtao
authors.initials: L
authors.lastname: Li
authors.affiliation: From the Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Ren
authors.initials: R
authors.lastname: Miao
authors.affiliation: From the Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Xuan
authors.initials: X
authors.lastname: Jia
authors.affiliation: From the Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Ward
authors.affiliation: From the Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132 jerry.kaplan@path.utah.edu.
authors.forename: Jerry
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006706:Homeostasis; D017136:Ion Transport; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C089360:CCC1 protein, S cerevisiae; D027682:Cation Transport Proteins; C109160:MMT1 protein, S cerevisiae; C109161:MMT2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron
keywords: Iron; Metal Homeostasis; Mitochondria; Oxygen Radicals; Transport Metal