Blood, 1 May 2003, Vol. 101, No. 9, pp. 3344-3344
Disentangling iron regulatory networks
Imbalances of iron homeostasis underlie some very frequent
clinical conditions, including iron-deficient anemia and
hereditary hemochromatosis, the latter being possibly the most common
inherited disorder in people of northern European origin leading to
progressive iron overload and subsequent organ damage. The
orchestration of cellular iron homeostasis is, thus, a leading priority
for organisms which can be referred to the crucial role of
iron for oxygen transport, for cellular energy supply, for function as
a cofactor of enzymes involved in oxidative phosphorylation, for DNA
synthesis due to the metal's role in ribonucleotide reductase, for
cellular differentiation by influencing the activity of cyclins, for
immune function by modulating cytokine activities and lymphocyte
proliferation, or for redox regulation in being a catalyst for radical formation.
With the increasing number of iron-susceptible target genes and the
identification of divergent fine-tuners of iron homeostasis, the iron
regulatory networks have become more difficult to survey.
In this issue, Muckenthaler and coworkers (page 3690) present a study
employing a microarray technique to screen for iron inducible genes by
means of a self-designed "iron chip." The functionality and reliability of this method has been underscored by the authors upon
investigation of the effect of various modulators of iron homeostasis
such as iron salts, nitric oxide, or hydrogen peroxide on the
expression of iron controlled genes. Studies such as this may open the
door to a new area in iron research in which screening of an
enormous number of target genes toward iron-mediated regulation can
easily be performed. Subsequent functional investigations will then
provide more insights into the regulatory networks of iron biology
under physiologic and pathologic conditions. Finally, "iron chips"
may turn out to be of practical value in clinics, for example, to
screen for inherited or acquired defects of iron homeostasis and its
metabolic consequences.
Günter Weiss
University of
Innsbruck
