title: Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria.
abstract: Steady-state concentrations of mitochondrial Mg(2+) previously have been shown to vary with the expression of Mrs2p, a component of the inner mitochondrial membrane with two transmembrane domains. While its structural and functional similarity to the bacterial Mg(2+) transport protein CorA suggested a role for Mrs2p in Mg(2+) influx into the organelle, other functions in cation homeostasis could not be excluded. Making use of the fluorescent dye mag-fura 2 to measure free Mg(2+) concentrations continuously, we describe here a high capacity, rapid Mg(2+) influx system in isolated yeast mitochondria, driven by the mitochondrial membrane potential Deltapsi and inhibited by cobalt(III)hexaammine. Overexpression of Mrs2p increases influx rates 5-fold, while the deletion of the MRS2 gene abolishes this high capacity Mg(2+) influx. Mg(2+) efflux from isolated mitochondria, observed with low Deltapsi only, also requires the presence of Mrs2p. Cross-linking experiments revealed the presence of Mrs2p-containing complexes in the mitochondrial membrane, probably constituting Mrs2p homo- oligomers. Taken together, these findings characterize Mrs2p as the first molecularly identified metal ion channel protein in the inner mitochondrial membrane.
authors.affiliation: Vienna Biocenter, Institute of Microbiology and Genetics, University of Vienna, Dr Bohrgasse, A-1030 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Kolisek
authors.forename: Gabor
authors.initials: G
authors.lastname: Zsurka
authors.forename: Jozef
authors.initials: J
authors.lastname: Samaj
authors.forename: Julian
authors.initials: J
authors.lastname: Weghuber
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Schweyen
authors.forename: Monika
authors.initials: M
authors.lastname: Schweigel
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003035:Cobalt / Q000037:antagonists & inhibitors; D003432:Cross-Linking Reagents / Q000737:chemistry; D004586:Electrophoresis; D016257:Fura-2 / Q000031:analogs & derivatives*; D017353:Gene Deletion; D005800:Genes, Fungal; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels; D008274:Magnesium / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D007473:Ion Channels; C114838:MRS2 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C058776:2-(2-(5-carboxy)oxazole)-5-hydroxy-6-aminobenzofuran-N,N,O-triacetic acid; C030862:cobalt ammonium complex; D003035:Cobalt; D008274:Magnesium; D016257:Fura-2