dictyNews
Electronic Edition
Volume 48, number 9
May 6, 2022

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=========
Abstracts
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Iron metabolism in the social amoeba Dictyostelium discoideum: 
a role for Ferric Chelate Reductases

Barbara Peracino1*, Valentina Monica2, Luca Primo2, Enrico Bracco2 
and Salvatore Bozzaro 1 

1 Department of Clinical and Biological Sciences, University of 
Torino, AOU S. Luigi, Orbassano 10043, Italy; 2 Department of 
Oncology, University of Turin, 10060 Candiolo, Italy.
* Correspondence should be addressed to: [log in to unmask]

Key words: Ferric chelate reductase, Dictyostelium discoideum, 
Iron metabolism, Iron binding proteins, Nramp1



European Journal of Cell Biology, in press pre=prrof
Available online 28 April 2022, 151230


Iron is the most abundant transition metal in all living
organisms and is essential for several cellular activities, 
including respiration, oxygen transport, energy production and 
regulation of gene expression. Iron starvation is used by 
professional phagocytes, from Dictyostelium to macrophages, 
as a form of defence mechanism against intracellular pathogens. 
Previously, we showed that Dictyostelium cells express the 
proton-driven iron transporter Nramp1 (Natural Resistance-
Associated Macrophage Protein 1) and the homolog NrampB 
(Nramp2) in membranes of macropinosomes and phagosomes or
 of the contractile vacuole network, respectively. The Nramp-driven 
transport of iron across membranes is selective for ferrous ions. 
Since iron is mostly present as ferric ions in growth media and 
in engulfed bacteria, we have looked for proteins with ferric 
reductase activity. The Dictyostelium genome does not encode 
for classical STEAP (Six-Transmembrane Epithelial Antigen of 
Prostate) ferric reductases, but harbours three genes encoding 
putative ferric chelate reductase belonging to the Cytochrome 
b561 family containing a N terminus DOMON domain (DOpamine 
beta-MONooxygenase N-terminal domain). We have cloned the 
three genes, naming them fr1A, fr1B and fr1C.  fr1A and fr1B are 
mainly expressed in the vegetative stage while fr1C is highly 
expressed in the post aggregative stage. All three reductases 
are localized in the endoplasmic reticulum, but Fr1A is also 
found in endolysosomal vesicles, in the Golgi and, to a much 
lower degree, in the plasma membrane, whereas Fr1C is 
homogeneously distributed in the plasma membrane and in 
macropinosomal and phagosomal membranes.To gain insight in 
the function of the three genes we generated KO mutants, but 
gene disruption was successful only for two of them (fr1A and 
fr1C), being very likely lethal for fr1B. fr1A- shows a slight delay 
in the aggregation stage of development, while fr1C- gives rise 
to large multi-tipped streams during aggregation and displays 
a strong delay in fruiting body formation. The two single mutants 
display altered cell growth under conditions of ferric ions 
overloading and, in the ability to reduce Fe3+, confirming a role 
of these putative ferric reductases in iron reduction and transport 
from endo-lysosomal vesicles to the cytosol.


Submitted by Barbara Peracino [[log in to unmask]]
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[End dictyNews, volume 48, number 9]