Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria

Heeyong Yoon, Yan Zhang, Jayashree Pain, Elise R. Lyver, Emmanuel Lesuisse, Debkumar Pain, Andrew Dancis

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Mitochondria transport and utilize iron for the synthesis of haem and Fe-S clusters. Although many proteins are known to be involved in these processes, additional proteins are likely to participate. To test this hypothesis, in the present study we used a genetic screen looking for yeast mutants that are synthetically lethal with the mitochondrial iron carriers Mrs3 and Mrs4. Several genes were identified, including an isolate mutated for Yfh1, the yeast frataxin homologue. All such triple mutants were complemented by increased expression of Rim2, another mitochondrial carrier protein. Rim2 overexpression was able to enhance haem and Fe-S cluster synthesis in wildtype or Δmrs3/Δmrs4 backgrounds. Conversely Rim2 depletion impaired haem and Fe-S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds, indicating a unique requirement for this mitochondrial transporter for these processes. Rim2 was previously shown to mediate pyrimidine exchange in and out of vesicles. In the present study we found that isolated mitochondria lacking Rim2 exhibited concordant iron defects and pyrimidine transport defects, although the connection between these two functions is not explained. When organellarmembranes were ruptured to bypass iron transport, haem synthesis from added iron and porphyrin was still markedly deficient in Rim2-depleted mitochondrial lysate. The results indicate that Rim2 is a pyrimidine exchanger with an additional unique function in promoting mitochondrial iron utilization.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalBiochemical Journal
Volume440
Issue number1
DOIs
StatePublished - Nov 15 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Haem
  • Iron
  • Iron-sulfur
  • Mitochondrial carrier protein
  • Mitochondrion
  • Pyrimidine

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