Ion channel identified as key factor in iron metabolism

by Ludwig Maximilian University of Munich

edited by Gaby Clark, reviewed by Robert Egan

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

Iron metabolism disorders are 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 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. The study is published in the journal Proceedings of the National Academy of Sciences.

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 TPC1 activity influences both the absorption of iron from the plasma membrane and the pH in certain cell organelles (called endosomes) that release iron into the cytosol depending on pH. "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," says Grimm.

Publication details

Rebecca Deutsch et al, TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status, Proceedings of the National Academy of Sciences (2026). DOI: 10.1073/pnas.2602941123

Journal information: Proceedings of the National Academy of Sciences

Key medical concepts

Iron Deficiencies

Clinical categories

Endocrinology Provided by Ludwig Maximilian University of Munich Who's behind this story?

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