Factors affecting the adenosine triphosphate induced release of iron from transferrin

Carver, Franklin J.; Frieden, Earl

doi:10.1021/bi00594a024

Cited by 56 publications

(16 citation statements)

References 14 publications

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“…tion of transferrin, but on the concentration of iron [29]. The same applies to the uptake of iron by reticulocytes [41], and as shown here to the uptake of transferrin iron by mitochondria (Fig.…”

Section: Discussionsupporting

confidence: 65%

Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria Mediated by Phosphate Compounds

Konopka¹,

Romslo

1980

European Journal of Biochemistry

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1. Isolated rat-liver mitochondria accumulate iron from transferrin at neutral pH by a mechanism which is markedly stimulated by small-molecular-weight polyphosphate compounds. The efficiency of the phosphate compounds decreases in the order: pyrophosphate > ATP > GTP > 2,3-bis-(phospho)glycerate > phosphate.2. The uptake has a very low energy dependence, and it does not depend on the hydrolysis of ATP or the saturation of transferrin, but it increases in parallel to the concentration of iron to reach a saturation level of 800-1200 pmol iron/mg protein.3 . Following a chase with unlabelled transferrin, ('251)-labelled transferrin bound to the mitochondria remains constant, whereas the progressive uptake of 59Fe levels off.4. During reincubation of iron-loaded mitochondria up to 30% of the iron is mobilized in the presence of ascorbate and ATP (or apotransferrin).5. The results suggest that iron is mobilized from transferrin by the polyphosphate compounds outside the mitochondria and taken up by the mitochondria in a subsequent reaction.The ferrochelatase reaction represents the ultimate destination for the major part of iron entering the cell. Although it has been claimed that the ferrochelatase resides in part [l] or exclusively in the cytosol [2] most investigators agree that the ferrochelatase is a particulate enzyme confined to the mitochondria [3-51, tentatively on the M-side of the inner membrane [6-81 and depending on unsaturated phospholipids for full activity [9]. Hence, to reach the ferrochelatase iron has to penetrate the mitochondria1 membrane systems.The mechanism(s) by means of which iron is transported across the cytosol, from the plasma membrane to the mitochondria is largely unknown, as is the nature of the cytosol iron-binding ligands. Controversy exists as to whether iron is released from transferrin at the plasma membrane [lo, to operate on the main pathway of iron to the niitochondria in vivo. The uptake of iron by isolated mitochondria has been described, using iron-ATP [18], iron-hydroxyquinoline [19] or iron-sucrose [20] as the iron donor compound. A coherent picture, however, has not emerged.The importance of transferrin as an iron-donor directly to the mitochondria has been emphasized [14,16]. As yet, however, there are only a few studies dealing with the utilization of transferrin iron by isolated mitochondria. Barnes et al. [21] concluded from experiments with sonicated mitochondria that neither transferrin not ferritin functioned as substrate to the ferrochelatase reaction. Ulvik et al. [22] and Koller et al. [23] found that iron was mobilized from transferrin by a mechanism sensitive to uncoupler, high pH and haemin. The release process operated at a rate below that necessary to cope with the ferrochelatase and also at a pH outside that occurring in vivo. It was concluded that transferrin was not a suitable donor of iron to mitochondria. More recently, Konopka [24] and Konopka and Turska [25] reported that rat liver mitochondria accumulated iron from transferrin at a signifi...

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Section: Discussionsupporting

confidence: 65%

Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria Mediated by Phosphate Compounds

Konopka¹,

Romslo

1980

European Journal of Biochemistry

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“…However, iron mobilized from transferrin by pyrophosphate is in the ferric form [9,11,14] and it should therefore not be readily chelatable by bathophenanthroline sulphonate. The reason for this apparent discrepancy is shown in Fig.…”

Section: Effect Of Ferrous Iron Chelutors On the Uptakp Of Ironmentioning

confidence: 99%

“…Pyrophosphate and ATP are the two polyphosphate compounds most extensively studied, but the molecular mechanismfs) by which they operate remains speculative [Ill. The rate of removal of iron, which seems to be in the ferric form [9,14], depends on the concentration of polyphosphates [5,7,9], the concentration of H + [9,10], the temperature [9], the ionic composition of the incubation medium [9,14], and the presence of a reductant and a second acceptor of iron, be it a ferric [5,12] or a ferrous iron chelator [9,11,12].…”

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confidence: 99%

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Studies on the Mechanism of Pyrophosphate‐Mediated Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria

Konopka¹,

Romslo

1981

European Journal of Biochemistry

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1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein-' h-', or approximately 60"/, of the amount of iron mobilized from transferrin.2. The uptake declines if respiration is inhibited, substrate is deleted, or the experiments are run under anaerobic conditions. Substrate depletion and respiratory inhibitors are less inhibitory under anaerobic conditions.3. More than SO"/, of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30 % of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5.The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous iron thus formed is available for heme synthesis.

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“…The intracellu lar environment of transferrin has a pH of about 5 and it has been suggested that this accounts for the iron release [1,2]. However, the acid-stable site of transferrin does not release its iron at pH 5 [3]; more over, when intracellular acidification is blocked, 80% of transferrin's iron is still released [4].…”

Section: Introductionmentioning

confidence: 99%

Iron Binding to Apotransferrin

Weaver¹,

Pollack²

1990

Acta Haematol

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The classic analysis of metal transfer between ligands suggests that the metal-binding ligand (M-L1) and the uncomplexed ligand (L2) form a mixed complex (L2-M-L1), and that transfer is effected with the dissociation of this complex to L2-M and L1. Spectroscopic data suggested that such mixed complexes formed when pyrophosphate-Fe and acetohydroxamate-Fe were added to apotransferrin: the initial species had a different absorbance maximum than the final transferrin-iron complex. We now show that similar spectroscopic changes are seen when free ferrous iron or iron liganded to ATP, citrate or nitrilotriacetate are added to apotransferrin. The evolving spectrum on the addition of iron to apotransferrin may thus reflect iron binding per se rather than the formation of a mixed ligand complex.

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Factors affecting the adenosine triphosphate induced release of iron from transferrin

Cited by 56 publications

References 14 publications

Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria Mediated by Phosphate Compounds

Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria Mediated by Phosphate Compounds

Studies on the Mechanism of Pyrophosphate‐Mediated Uptake of Iron from Transferrin by Isolated Rat‐Liver Mitochondria

Iron Binding to Apotransferrin

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