Deletion of the Mitochondrial Carrier Genes MRS3 andMRS4 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 ΔYFH1 than in wild-type strain. However, although in a ΔYFH1ΔMRS3ΔMRS4 strain, the intracellular 55Fe content is extremely high, the mitochondrial iron concentration is decreased to almost wild-type levels. Moreover, ΔYFH1ΔMRS3ΔMRS4 cells grown in high iron media do not lose their mitochondrial genome. Conversely, a ΔYFH1 strain overexpressing MRS4 has an increased mitochondrial iron content and no mitochondrial genome. Therefore, MRS4 is required for mitochondrial iron accumulation in ΔYFH1 cells. Expression of the iron regulon and intracellular 55Fe content are higher in a ΔMRS3ΔMRS4 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 ofMRS4 in iron import into mitochondria is discussed.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-07-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M111789200PMID 12006577
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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