Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis.
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Yoon T, Cowan JA
Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis.
J Biol Chem. 2004 Jun 18;279(25):25943-6. Epub 2004 Apr 27.
- PubMed ID
- 15123683 [ View in PubMed]
- Abstract
Human ferrochelatase, a mitochondrial membrane-associated protein, catalyzes the terminal step of heme biosynthesis by insertion of ferrous iron into protoporphyrin IX. The recently solved x-ray structure of human ferrochelatase identifies a potential binding site for an iron donor protein on the matrix side of the homodimer. Herein we demonstrate Hs holofrataxin to be a high affinity iron binding partner for Hs ferrochelatase that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis. A general regulatory mechanism for mitochondrial iron metabolism is described that defines frataxin involvement in both heme and iron-sulfur cluster biosyntheses. In essence, the distinct binding affinities of holofrataxin to the target proteins, ferrochelatase (heme synthesis) and ISU (iron-sulfur cluster synthesis), allows discrimination between the two major iron-dependent pathways and facilitates targeted heme biosynthesis following down-regulation of frataxin.