Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis

Yan Zhang, Elise R. Lyver, Eiko Nakamaru-Ogiso, Heeyong Yoon, Boominathan Amutha, Dong Woo Lee, Erfei Bi, Tomoko Ohnishi, Fevzi Daldal, Debkumar Pain, Andrew Dancis

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116 Citations (Scopus)

Abstract

In a forward genetic screen for interaction with mitochondrial iron carrier proteins in Saccharomyces cerevisiae, a hypomorphic mutation of the essential DRE2 gene was found to confer lethality when combined with Δmrs3 and Δmrs4. The dre2 mutant or Dre2-depleted cells were deficient in cytosolic Fe/S cluster protein activities while maintaining mitochondrial Fe/S clusters. The Dre2 amino acid sequence was evolutionarily conserved, and cysteine motifs (CX2CXC and twin CX2C) in human and yeast proteins were perfectly aligned. The human Dre2 homolog (implicated in blocking apoptosis and called CIAPIN1 or anamorsin) was able to complement the nonviability of a Δdre2 deletion strain. The Dre2 protein with triple hemagglutinin tag was located in the cytoplasm and in the mitochondrial intermembrane space. Yeast Dre2 overexpressed and purified from bacteria was brown and exhibited signature absorption and electron paramagnetic resonance spectra, indicating the presence of both [2Fe-2S] and [4Fe-4S] clusters. Thus, Dre2 is an essential conserved Fe/S cluster protein implicated in extramitochondrial Fe/S cluster assembly, similar to other components of the so-called CIA (cytoplasmic Fe/S cluster assembly) pathway although partially localized to the mitochondrial intermembrane space.

Original languageEnglish
Pages (from-to)5569-5582
Number of pages14
JournalMolecular and cellular biology
Volume28
Issue number18
DOIs
Publication statusPublished - 2008 Sep 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Zhang, Y., Lyver, E. R., Nakamaru-Ogiso, E., Yoon, H., Amutha, B., Lee, D. W., Bi, E., Ohnishi, T., Daldal, F., Pain, D., & Dancis, A. (2008). Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis. Molecular and cellular biology, 28(18), 5569-5582. https://doi.org/10.1128/MCB.00642-08