Molecular dissection of intracellular iron regulation

Iron is an essential metal for organisms and is, in turn, toxic, which means that intracellular availability and its storage must be firmly subject to regulation. From prokaryotes (bacteria) to higher, more complex organisms, iron deficiency triggers complicated genetic responses to promote intracellular iron absorption and its use.

The Oxidative Stress and Cell Cycle research group at the Department of Experimental and Health Sciences (CEXS) at UPF, led by Elena Hidalgo and José Ayté , both co-authors of a paper that has been published in the journal PLOSGenetics in March studies the response of Schizosaccharomyces pombe yeast to deal with iron deprivation and the different types of regulation of cell gene expression programmes. Postdoctoral researchers Javier Encinar del Dedo and Natalia Gabrielli are first authors of this work.

In this study, the authors have performed a "complete molecular dissection of the components and the events that govern this cell signalling cascade in S. pombe yeast", explains Hidalgo.

The cell adapts according to the bioavailability of iron

Each cell type responds in different ways to the scarcity of iron. In eukaryotic organisms such as unicellular S. pombe, two transcriptional repressors, Php4 and Fep1, mediate the regulation of this process, blocking usage/storage and promoting iron import, respectively, so that when this essential metal is scarce Php4 must be activated and Fep1 inactivated.

A single protein complex, Grx4-Fra2, is responsible for regulating the two repressors. Thus, the dimer of proteins Grx4-Fra2, of which iron is an essential element, detects the depletion of the metal inside the cell, activates Php4 and inactivates Fep1, with the ultimate aim of promoting an adaptive survival response to the shortage of iron.

Hidalgo and Ayté stress that "all the proteins of these signalling cascades (Grx4, Fra2, Fep1 and Php4) contain iron in their structure, so that these proteins can regulate the lack of iron in the cell by losing the metal from their own molecule".

These complex molecular mechanisms help the cell to adapt to the fluctuations of this toxic metal so that its import is only activated when there is shortage of iron to prevent its accumulation and toxicity.

Reference work:

Encinar del Dedo J, Gabrielli N, Carmona M, Ayté J, Hidalgo E., (2015), " A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast", PLOS Genetics, 25;11(3):e1005106. doi: 10.1371/journal.pgen.1005106.