The ferroxidase activity of yeast frataxin

Sungjo Park, Oleksandr Gakh, Steven M. Mooney, Grazia Isaya

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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 (α48) that accumulates iron in a water-soluble form. Here, two distinct iron oxidation reactions are shown to take place during the initial assembly step (α → α3). 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, α3, 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 mYfhlp 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.

Original languageEnglish (US)
Pages (from-to)38589-38595
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number41
DOIs
StatePublished - Oct 11 2002

Fingerprint

Ceruloplasmin
Yeast
Iron
Yeasts
Stoichiometry
Oxidation
Oligomerization
Oligomers
Gel Chromatography
Respiration
Gels
Maintenance
Degradation
Water
frataxin
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Park, S., Gakh, O., Mooney, S. M., & Isaya, G. (2002). The ferroxidase activity of yeast frataxin. Journal of Biological Chemistry, 277(41), 38589-38595. https://doi.org/10.1074/jbc.M206711200

The ferroxidase activity of yeast frataxin. / Park, Sungjo; Gakh, Oleksandr; Mooney, Steven M.; Isaya, Grazia.

In: Journal of Biological Chemistry, Vol. 277, No. 41, 11.10.2002, p. 38589-38595.

Research output: Contribution to journalArticle

Park, S, Gakh, O, Mooney, SM & Isaya, G 2002, 'The ferroxidase activity of yeast frataxin', Journal of Biological Chemistry, vol. 277, no. 41, pp. 38589-38595. https://doi.org/10.1074/jbc.M206711200
Park, Sungjo ; Gakh, Oleksandr ; Mooney, Steven M. ; Isaya, Grazia. / The ferroxidase activity of yeast frataxin. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 41. pp. 38589-38595.
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