Ion channel TPC1 identified as key regulator of iron homeostasis

Researchers have deciphered the role of an ion channel in iron homeostasis, opening up new possibilities for treating iron metabolism disorders.

Iron metabolism disorders are very common. Iron deficiency and the resulting anemia affect millions of people, while the genetic iron overload disorder hemochromatosis is one of the most common hereditary diseases in Europe. Hemochromatosis is a life-threatening disease that can lead to severe organ damage without early diagnosis and treatment.

A team led by LMU/Oxford pharmacologist Professor Christian Grimm has investigated the molecular mechanisms of iron metabolism. Using patch-clamp experiments – a technique for measuring ion channel activity – the researchers showed in a mouse model that the ion channel TPC1 plays a key role and elucidated its mechanisms.

If TPC1 changes as the result of a specific genetic mutation, its activity greatly increases – with the consequence that mice accumulate too much iron in their bodies. Conversely, if the channel is completely absent, the animals develop iron deficiency. Laboratory experiments showed that after activation, the mutated forms are considerably more active than normal ones – both in human and mouse TPC1 channels. In addition, the researchers demonstrated that TCP1 activity influences both the absorption of iron from the plasma membrane and the pH value in certain cell organelles (called endosomes) that release iron into the cytosol based on pH value.

Our study thus furnishes new insights into the regulation of iron homeostasis. In the long term, it could open up new approaches for the treatment of diseases related to iron deficiency or iron overload.”

Professor Christian Grimm, LMU/Oxford pharmacologist