title: A specific role of the yeast mitochondrial carriers MRS3/4p in mitochondrial iron acquisition under iron-limiting conditions.
abstract: The yeast genes MRS3 and MRS4 encode two members of the mitochondrial carrier family with high sequence similarity. To elucidate their function we utilized genome-wide expression profiling and found that both deletion and overexpression of MRS3/4 lead to up-regulation of several genes of the "iron regulon." We therefore analyzed the two major iron-utilizing processes, heme formation and Fe/S protein biosynthesis in vivo, in organello (intact mitochondria), and in vitro (mitochondrial extracts). Radiolabeling of yeast cells with 55Fe revealed a clear correlation between MRS3/4 expression levels and the efficiency of these biosynthetic reactions indicating a role of the carriers in utilization and/or transport of iron in vivo. Similar effects on both heme formation and Fe/S protein biosynthesis were seen in organello using mitochondria isolated from cells grown under iron-limiting conditions. The correlation between MRS3/4 expression levels and the efficiency of the two iron-utilizing processes was lost upon detergent lysis of mitochondria. As no significant changes in the mitochondrial membrane potential were observed upon overexpression or deletion of MRS3/4, our results suggest that Mrs3/4p carriers are directly involved in mitochondrial iron uptake. Mrs3/4p function in mitochondrial iron transport becomes evident under iron-limiting conditions only, indicating that the two carriers do not represent the sole system for mitochondrial iron acquisition.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch Str 6, 35033 Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.forename: Jochen A
authors.initials: JA
authors.lastname: Stadler
authors.forename: Nadine
authors.initials: N
authors.lastname: Richhardt
authors.forename: Andreas
authors.initials: A
authors.lastname: Seubert
authors.forename: Thomas
authors.initials: T
authors.lastname: Eickhorst
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Schweyen
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Wiesenberger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000502:physiology*; D027682:Cation Transport Proteins; D003600:Cytosol / Q000378:metabolism; D017353:Gene Deletion; D016681:Genome, Fungal; D006418:Heme / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; C066985:MRS3 protein, S cerevisiae; C066986:MRS4 protein, S cerevisiae; D024101:Mitochondrial Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D006418:Heme; D000255:Adenosine Triphosphate; D007501:Iron