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J. Biol. Chem., Vol. 277, Issue 41, 38589-38595, October 11, 2002
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From the Departments of Pediatric & Adolescent Medicine and
Biochemistry & Molecular Biology, Mayo Clinic and Foundation,
Rochester, Minnesota 55905
Frataxin is required for maintenance of normal
mitochondrial iron levels and respiration. The mature form of yeast
frataxin (mYfh1p) assembles stepwise into a multimer of 840 kDa
(
The Ferroxidase Activity of Yeast Frataxin*
48) that accumulates iron in a water-soluble
form. Here, two distinct iron oxidation reactions are shown to take
place during the initial assembly step ( 
3). A
ferroxidase reaction with a stoichiometry of 2 Fe(II)/O2 is
detected at Fe(II)/mYfh1p ratios of 
0.5. Ferroxidation is
progressively overcome by autoxidation at Fe(II)/mYfh1p ratios of
>0.5. Gel filtration analysis indicates that an oligomer of mYfh1p,
3, is responsible for both reactions. The observed 2 Fe(II)/O2 stoichiometry implies production of
H2O2 during the ferroxidase reaction. However,
only a fraction of the expected total H2O2 is
detected in solution. Oxidative degradation of mYfh1p during the
ferroxidase reaction suggests that most H2O2
reacts with the protein. Accordingly, the addition of mYfh1p to a
mixture of Fe(II) and H2O2 results in
significant attenuation of Fenton chemistry. Multimer assembly is fully
inhibited under anaerobic conditions, indicating that mYfh1p is
activated by Fe(II) in the presence of O2. This combination
induces oligomerization and mYfh1p-catalyzed Fe(II) oxidation, starting
a process that ultimately leads to the sequestration of as many as 50 Fe(II)/subunit inside the multimer.
*
This work was supported by Grant AG15709 from the NIA,
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Mayo Clinic and
Foundation, 200 First St. SW, Stabile 7-52, Rochester, MN 55905. Tel.: 507-266-0110; Fax: 507-266-9315; E-mail:
isaya@mayo.edu.
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