Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain.
The mitochondrial solute carriers Mrs3p and Mrs4p were originally isolated as multicopy suppressors of intron splicing defects. We show here that MRS4 is co-regulated with the iron regulon genes, and up-regulated in a strain deficient for Yfh1p, the yeast homologue of human frataxin. Using in vivo 55Fe cell radiolabeling we show that in glucose-grown cells mitochondrial iron accumulation is 5-15 times higher in deltaYFH1 than in wild-type strain. However, although in a deltaYFH1deltaMRS3deltaMRS4 strain, the intracellular 55Fe content is extremely high, the mitochondrial iron concentration is decreased to almost wild-type levels. Moreover, deltaYFH1deltaMRS3deltaMRS4 cells grown in high iron media do not lose their mitochondrial genome. Conversely, a deltaYFH1 strain overexpressing MRS4 has an increased mitochondrial iron content and no mitochondrial genome. Therefore, MRS4 is required for mitochondrial iron accumulation in deltaYFH1 cells. Expression of the iron regulon and intracellular 55Fe content are higher in a deltaMRS3deltaMRS4 strain than in the wild type. Nevertheless, the mitochondrial 55Fe content, a balance between iron uptake and exit, is decreased by a factor of two. Moreover, 55Fe incorporation into heme by ferrochelatase is increased in an MRS4-overexpressing strain. The function of MRS4 in iron import into mitochondria is discussed.
Foury
Francoise
F
Unité de Biochimie Physiologique, Place Croix du Sud, 2-20, 1348 Louvain-la-Neuve, Belgium. foury@fysa.ucl.ac.be
Roganti
Tiziana
T
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D027682:Cation Transport Proteins; D002455:Cell Division; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D016681:Genome, Fungal; D033862:Iron-Binding Proteins; D007700:Kinetics; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D000096923:Frataxin
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D017931:DNA Primers; D004272:DNA, Mitochondrial; D005656:Fungal Proteins; D033862:Iron-Binding Proteins; D024101:Mitochondrial Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin; C066985:MRS3 protein, S cerevisiae; C066986:MRS4 protein, S cerevisiae