Is Hydrogen Peroxide Produced during Iron(II) Oxidation in Mammalian Apoferritins?

Zhao, Guanghua; Bou-Abdallah, Fadi; Yang, Xiaoke; Arosio, Paolo; Chasteen, N. Dennis

doi:10.1021/bi011052j

Cited by 67 publications

(132 citation statements)

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“…ApoHuHF concentrations were determined by absorbance at 280 nm (21). Other protein concentrations were determined by Advanced Protein Assay (http://cytoskeleton.com) with BSA as a standard.…”

Section: Methodsmentioning

confidence: 99%

“…The above H-chain catalyzed reaction proceeds through a µ-1, 2- (14)(15)(16)(17)(18)(19)(20)(21). The fate of the H 2 O 2 produced in eq 1 has been an open question because some of it is consumed in a subsequent undefined reaction(s) (21,22).…”

mentioning

confidence: 99%

“…The fate of the H 2 O 2 produced in eq 1 has been an open question because some of it is consumed in a subsequent undefined reaction(s) (21,22).…”

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confidence: 99%

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Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide

et al. 2003

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Human ferritins sequester and store iron as a stable FeOOH (s) mineral core within a protein shell assembled from 24 subunits of two types, H and L. Core mineralization in recombinant H-and L-subunit homopolymer and heteropolymer ferritins and several site-directed H-subunit variants was investigated to determine the iron oxidation/hydrolysis chemistry as a function of iron flux into the protein.Stopped-flow absorption spectrometry, UV spectrometry, and electrode oximetry revealed that the mineral core forms by at least three pathways, not two as previously thought. They correspond to the ferroxidase, mineral surface, and the Fe(II) + H 2 O 2 detoxification reactions, respectively:

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confidence: 99%

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Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide

et al. 2003

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“…Detection of H 2 O 2 , Protein Carbonyls, and Malondialdehyde-To determine the production of H 2 O 2 by electrode oximetry, catalase (2,600 -3,900 units) was added to 0.465 ml of 96 M mYfh1p in 10 mM HEPES-KOH, pH 7.0, either before or after the addition of Fe(II), and the O 2 consumption and Fe(II)/O 2 stoichiometry for the completed reaction were measured (29). Production of H 2 O 2 was further measured by the Amplex Red hydrogen peroxide/peroxidase assay kit from Molecular Probes, Inc. (Eugene, OR) (29).…”

Section: Methodsmentioning

confidence: 99%

“…Production of H 2 O 2 was further measured by the Amplex Red hydrogen peroxide/peroxidase assay kit from Molecular Probes, Inc. (Eugene, OR) (29). All of the reactions (1 ml) were performed in vials sealed with a rubber septum according to the manufacturer's protocol except that 50 mM HEPES-KOH, pH 7.0, was used instead of 50 mM phosphate pH 7.4 buffer (29).…”

Section: Methodsmentioning

confidence: 99%

The Ferroxidase Activity of Yeast Frataxin

Park

Gakh

Mooney

et al. 2002

Journal of Biological Chemistry

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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 (␣ 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 ␣ 3 ). A ferroxidase reaction with a stoichiometry of 2 Fe(II)/O 2 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 two major iron-utilizing processes in the cell, production of heme by ferrochelatase and the iron-sulfur cluster biosynthetic pathway, reside in the mitochondrial matrix. Mitochondria contain micromolar concentrations of chelatable iron (1), i.e. iron that is not yet complexed in heme or iron-sulfur clusters and is bioavailable (2). Keeping this iron pool in soluble and nontoxic form represents a remarkable biological challenge given the alkaline pH (3) and the high production of O 2. and H 2 O 2 (4) within mitochondria. Thus, the existence of proteins capable of handling iron safely within mitochondria was first postulated several decades ago (5). Recent studies have identified a handful of inner mitochondrial membrane proteins involved in mitochondrial iron transport (6 -8) as well as a mitochondrial matrix ferritin involved in iron storage (9). The mitochondrial matrix protein frataxin has been implicated in mitochondrial iron homeostasis (10, 11), but its precise function is still not known. Frataxin was first identified as the protein deficient in Friedreich ataxia, a neuro-and cardiodegenerative disease (12). Studies in Saccharomyces cerevisiae have shown that defects in yeast or human frataxin are associated with the accumulation of iron in mitochondria and oxidative damage to both mitochondrial and nuclear DNA as well as to the iron-sulfur centers of mitochondrial aconitase and other respiratory enzymes (10,14,15,34). Similarly, mouse models in which the frataxin gene is selectively inactivated in neuronal or cardiac tissue present multiple respiratory enzyme deficits and accumulate iron in mitochondria in a time-dependent manner (16). In agreement with these observations, evidence of abnormal cellular iron homeostasis, increased oxidative damage, and respiratory enzyme deficits has been reported for the human disease (reviewed in Ref. 17). It has been shown that frataxin defects result in impaired mitochondrial iron efflux (18), defective biosynthesis of iron-sulfur clusters (19,20), loss of ATP synthesis (21), and/or disabled antioxidant defenses (22), all conditions that could ultimately lead to mitochondrial iron accumulation and increased oxidative damage. We have proposed that the apparent involvement of frataxin in so many diverse processes could be explained if the basic function of this protein were to provide an iron storage mechanism to keep iron in a bioava...

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Iron Proteins for Storage & Transport & Their Synthetic Analogs

Lewin

Brun

Moore

2005

Encyclopedia of Inorganic Chemistry

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This article reviews proteins involved in iron metabolism. Brief descriptions are given of the biological contexts for the proteins discussed but the main emphasis is on chemical and structural aspects of them. Iron is essential to almost all forms of life, but its low bioavailability and toxicity mean that they require sophisticated mechanisms to transport it. Mammals acquire heme and nonheme iron via proteins in the gut wall, and transport it around the body using serum transferrin, for ferric iron, and hemopexin, for heme. Microbes have an active iron uptake mechanism involving small iron chelators called siderophores, for example, ferrichrome in Escherichia coli . Ferrichrome enters the cell via FhuA, a β‐barrel in the outer membrane. The periplasmic protein FhuD then transfers it to the FhuBC complex in the cytoplasmic membrane. FhuB forms a channel through which the ferric siderophore passes using energy supplied by FhuC. Once inside the cytoplasm the iron is removed from the ligand, possibly via reduction by FhuF. Some pathogenic bacteria have a similar system for heme uptake, secreting hemophores such as HasA, which can remove heme from hemoglobin. Other pathogens have outer membrane receptors that remove ferric iron from transferrin and transport it into the periplasm, where it is bound by ferric binding proteins that closely resemble a single lobe of transferrin. Following its acquisition, iron needs to be stored safely. The most widespread form of iron storage is the ferritin superfamily, which includes ferritin, bacterioferritin, and Dps. Ferritin is found in bacteria, plants, and animals and is a large shell made up of 24 subunits within which up to 4,500 ferric ions can be stored as a ferrihydrite mineral core. Bacterioferritin is found in bacteria and is closely related to ferritin, but contains up to 12 heme groups bound between pairs of subunits, which may play a role in iron release or electron storage. The bacterial protein Dps is smaller than ferritin, with 12 subunits forming the protein shell, and can hold up to 500 ferric ions. All of these proteins contain dinuclear iron sites that catalyze the oxidation of ferrous iron. An alternative form of iron storage is frataxin, found in mitochondria. Although not related to ferritin, this protein has the ability to form large aggregates that can store up to 50 ferric ions per monomer in a mineral core resembling those of ferritins.

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Is Hydrogen Peroxide Produced during Iron(II) Oxidation in Mammalian Apoferritins?

Cited by 67 publications

References 36 publications

Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide

Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide

The Ferroxidase Activity of Yeast Frataxin

Iron Proteins for Storage & Transport & Their Synthetic Analogs

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