2. Academic Validation
  3. Evolution of the human mitochondrial ABCB7 [2Fe-2S](GS)4 cluster exporter and the molecular mechanism of an E433K disease-causing mutation

Evolution of the human mitochondrial ABCB7 [2Fe-2S](GS)4 cluster exporter and the molecular mechanism of an E433K disease-causing mutation

  • Arch Biochem Biophys. 2021 Jan 15;697:108661. doi: 10.1016/j.abb.2020.108661.
Stephen A Pearson 1,  J A Cowan 2
Affiliations

Affiliations

  • 1 The Ohio State University Biophysics Program, The Ohio State University, 484 West 12thAvenue, Columbus, OH, 43210, United States.
  • 2 The Ohio State University Biophysics Program, The Ohio State University, 484 West 12thAvenue, Columbus, OH, 43210, United States; Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH, 43210, United States. Electronic address: https://chemistry.osu.edu/people/cowan.2.
PMID: 33157103 DOI: 10.1016/j.abb.2020.108661
Abstract

Iron-sulfur cluster proteins play key roles in a multitude of cellular processes. Iron-sulfur cofactors are assembled primarily in mitochondria and are then exported to the cytosol by use of an ABCB7 transporter. It has been shown that the yeast mitochondrial transporter Atm1 can export glutathione-coordinated iron-sulfur clusters, [2Fe-2S](SG)4, providing a source of cluster units for cytosolic iron-sulfur cluster assembly systems. This pathway is consistent with the endosymbiotic model of mitochondrial evolution where homologous Bacterial heavy metal transporters, utilizing metal glutathione adducts, were adapted for use in eukaryotic mitochondria. Herein, the basis for endosymbiotic evolution of the human cluster export protein (ABCB7) is developed through a BLAST analysis of transporters from ancient proteobacteria. In addition, a functional comparison of native human protein, versus a disease-causing mutant, demonstrates a key role for residue E433 in promoting cluster transport. Dysfunction in mitochondrial export of Fe-S clusters is a likely cause of the disease condition X-linked sideroblastic anemia.

Keywords

ABCB7; Atm1; Endosymbiosis; Mitochondrial exporter; [2Fe–2S](GS)(4) cluster complex.

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