Supply and demand

Scientists at the European Molecular Biology Laboratory have discovered that a group of proteins named IRPs ensure that the iron balance is maintained in cells and, as such, are essential for cell survival.

Most organisms need iron to survive, but too much iron is toxic and can cause fatal organ failure. The same is true inside cells, where iron balance must also be maintained.

In a study published in Cell Metabolism, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have shown that IRPs ensure the iron balance is maintained in cells. More specifically, the scientists found that IRPs are required for the functioning of mitochondria.

Mitochondria need iron to function, but they also convert iron into other chemical forms used throughout the cell: iron sulphur clusters and haem, one of the building blocks of haemoglobin. Thanks to new mouse models they engineered, the scientists were able to selectively shut down IRP function in specific cell types.

‘Mice whose liver cells can’t produce IRPs die of liver failure a few days after birth,’ says Bruno Galy, Staff Scientist in Matthias Hentze’s group at EMBL, who spearheaded the work. ‘The mitochondria in those cells have structural defects and don’t function properly, because they don’t have enough iron.’

In cells that cannot produce IRPs, the mechanisms for iron export and storage go into overdrive, while iron import is drastically reduced. This combination of factors leads to an iron shortage in the cell.

The role of IRPs is to ensure that there is enough iron available in the cell to sustain mitochondrial iron needs.

‘We have indications that this is probably a general process by which most cells control their iron content and secure mitochondrial iron sufficiency,’ Hentze concludes.

This might be a double-edged sword: there are situations in which mitochondria get iron but are not able to make use of it. This ultimately results in detrimental iron overloading of mitochondria.

This might underlie the pathology of several diseases, including inherited sideroblastic anaemias and the neurodegenerative disorder Friedreich’s ataxia, which the EMBL scientists are currently investigating.

Further reading

Galy, B. et al. (2010) Iron regulatory proteins secure mitochondrial iron sufficiency and function. Cell Metabolism, 12, 194–201

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