Regulatory mechanism of iron metabolism and its involvement in diseases
Iron is essential for virtually all cells where it plays an important role in many processes, e.g. DNA synthesis, respiration and oxygen transport. On the other hand, iron must be regulated tightly because iron has a high reactivity with oxygen to generate reactive oxygen species such as hydroxyl radicals, which can damage biomolecules including DNA and lipids. Defects in iron metabolism and resulting iron accumulation can lead to energy depletion and oxidative damage, which are increasingly implicated in degenerative diseases. Therefore both iron deficiency and overload can provoke deleterious effects on our health.
The team of Barbara Scheiber-Mojdehkar and Brigitte Sturm focus on two main aspects of iron regulation:
• Iron deficiency occurs often in patients undergoing regular dialysis. Therefore intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to treat renal anemia. Although available intravenous iron preparations are clinically effective, significant morbidity from both dose-dependent and -independent side effects have been reported.
We focus on the influence of intravenous iron compounds (in use or under development) on cellular iron metabolism.
• Iron accumulation occurs in a range of degenerative diseases. Here we work with a certain disease called Friedreich´s ataxia (FRDA) which is a genetic neurodegenerative disease that is the most common hereditary ataxia. FRDA has an estimated incidence of 1 in 30,000 people. Patients with FRDA suffer from progressive loss of neuronal and cardiac cells that result in wheelchair confinement, heart failure, and death at a young age. Onset of FRDA is on average at 10-15 years of age, but may be delayed to middle or later years of life.
This devastating disease is caused by the reduced expression of frataxin, a protein required to handle iron safely within the mitochondria. The exact function of frataxin is still unknown but was shown to play an essential role in iron metabolism and is required for assembly and activation of iron-sulfur clusters, heme biosynthesis, iron detoxification and antioxidant protection.
Therefore, frataxin deficiency results in widespread pleiotropic effects, including impaired energy metabolism, increased oxidative stress, neurodegeneration, and cardiotoxicity.
We focus on the expression pattern of frataxin, the regulation of frataxin levels and on the development of new therapies for Friedreich`s ataxia.