Abstract
There is evidence for an unexpected role of diferric transferrin as a terminal oxidase for the transplasma membrane oxidation of cytosolic NADH. In the original studies which showed the reduction of iron in transferrin by the plasma membranes NADH oxidase, the possible role of the reduction on iron uptake was emphasized. The rapid reoxidation of transferrin iron under aerobic conditions precludes a role for surface reduction at neutral pH for release of iron for uptake at the plasma membrane. The stimulation of cytosolic NADH oxidation by diferric transferrin indicates that the transferrin can act as a terminal oxidase for the transplasma membrane NADH oxidase or can bind to a site which activates the oxidase. Since plasma membrane NADH oxidases clearly play a role in cell signaling, the relation of ferric transferrin stimulation of NADH oxidase to cell control should be considered, especially in relation to the growth promotion by transferrin not related to iron uptake. The oxidase can also contribute to control of cytosolic NAD concentration, and thereby can activate sirtuins for control of ageing and growth.
Highlights
The remarkable diversity of oxidative activity at the plasma membrane has only recently been brought into focus
The diferric transferrin stimulated oxidase may require the reduced coenzyme Q oxidase [18, 24] and one of the known NADH dehydrogenases in the plasma membrane for the complete electron transfer chain from NADH to oxygen [19, 20, 25]
Since the plasma membrane NADH oxidase responds to growth factors like epidermal growth factor (EGF), it may have a role in signaling
Summary
The remarkable diversity of oxidative activity at the plasma membrane has only recently been brought into focus. The H2O2 generating capacity in plasma membrane of other types of cells has been recognized and proposed to be the basis for hormone and growth factor response, oxygen sensing [7], and microbicidal action [8,9,10,11,12]. These H2O2 generating systems have all been related to the NADPH oxidase GP91 phox Gp22 phox enzymes first recognized in neutrophils [5, 6]. The activation of the NADH oxidase by diferric transferrin and the relation to cellular control are the subjects of this paper
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