2018 January 23

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis

The Iron Metabolism, Regulation and Disease group publishes two new studies on iron disorders

Iron is an essential element for life in animals and people, who need a constant intake from their food.  But iron is not a substance that can function biologically in its simple form, it must form part of biological molecules for it to be taken up by the body, transported, stored and used for vital processes; for example it is incorporated into haemoglobin which allows red blood cells to transport oxygen.

There is a delicate balance of iron within individual cells, controlled by a very complex system.  Iron not needed immediately is stored in the form of different biological molecules in the liver and spleen, from where it is moved if the body needs to use more.  

Most of us are familiar with the idea that if we are short of iron we will have anaemia, however the complexity of the control system means that there are many possibilities for error and as well as there being many types of anaemias, with different causes and consequences there are many other diseases associated with an incorrect balance of iron in the body.  Some of these mean iron accumulates in different parts of the body and can lead to severe health problems.

The Iron Metabolism, Regulation and Disease group, led by Mayka Sanchez, studies the delicate mechanisms behind the control of iron in the body.  They investigate the substances involved in grabbing onto iron and moving it around the body and those controlling this movement.   They also study the small genetic changes that can disrupt different parts of this system and cause it to fail, leading to too much or too little iron.  The genetic changes are often hereditary, leading to families with the same condition.  Some of these diseases are rare, sometimes occurring in just a few families, but identifying the exact genetic change is essential for doctors to provide the best treatment as many diseases have similar symptoms, but different causes and treatments.

At the end of 2017 the group published the results of two pieces of research:

In the paper “The actin-binding protein profilin 2 is a novel regulator of iron homeostasis”, published in the high profile journal Blood, the group describes how a protein profilin 2, previously known to be involved in structural changes in cells is also involved in managing the iron balance.   Mice lacking this protein accumulated iron in several parts of their brains.

A paper titled “Functional characterization of a novel non-coding mutation "Ghent +49A > G" in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome” the group shone more light on a rare iron disorder called hyperferritinaemia-cataract syndrome.  Members of the family in the study suffer from cataracts caused by disruptions in control of the normal iron balance.   The scientists discovered a genetic mutation called Ghen+49A > G and a relationship between the severity of the cataracts and whether family members had one or two faulty copies of the gene.

Mayka Sanchez told us, “People with rare iron disorders suffer unpleasant symptoms and often find it very difficult to get a correct diagnosis for the problem.  We carry out our work in close conjunction with doctors and we provide them will tools to diagnose these unusual conditions so that they can provide the best treatments in each case.  Our work is very technical but very much centred on the patients.”

 

See the two new articles from the Iron  Metabolism, Regulation and Disease Group here:

Luscieti S, Galy B, Gutierrez L, Reinke M, Couso J, Shvartsman M, Di Pascale A, Witke W, Hentze MW, Pilo Boyl P, Sanchez M

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis

Blood 26 Oct 2017, 130 (17) 1934-1945. Epub 3 Ago 2017

 

Van de Sompele S, Pécheux L, Couso J, Meunier A, Sanchez M, De Baere E

Functional characterization of a novel non-coding mutation "Ghent +49A > G" in the iron-responsive element of L-ferritin causing hereditary hyperferritinaemia-cataract syndrome

Sci Rep. 2017 Dec 21;7(1):18025. doi: 10.1038/s41598-017-18326-6