Iron And Heme Metabolism

My research on iron metabolism ranges from cellular iron sensing to genetic iron disorders, non-invasive measurement of hepatic iron and the emerging RBC�liver axis.

Early work established iron regulatory protein 1 as a redox-sensitive regulator and showed how extracellular hydrogen peroxide alters cellular iron uptake. Subsequent studies examined hepcidin regulation by sustained low-level peroxide, hypoxia and hepatocyte�endothelial cell crosstalk.

Clinical projects included the first German family with hereditary hyperferritinemia-cataract syndrome and the development of room-temperature susceptometry for non-invasive quantification of hepatic iron.

Recent work extended this research from classical iron regulation to the role of red blood cells in hepatic iron loading. We were the first to demonstrate that hepatocytes can directly ingest entire oxidized red blood cells by efferocytosis. Together with erythrophagocytosis by macrophages and phosphatidylserine-dependent clearance by liver sinusoidal endothelial cells, these findings establish the liver as a central site of whole-red-cell clearance and provide a direct mechanism linking alcohol-mediated hemolysis to hepatic iron overload and progressive liver injury.

Selected publications

IRP1 activation by extracellular oxidative stress in the perfused rat liver. Mueller S et al. J Biol Chem. 2001;276(25):23192�23196.
Hyperferritinaemia-cataract syndrome: worldwide mutations and phenotype of an increasingly diagnosed genetic disorder. Millonig G et al. Hum Genomics. 2010;4(4):250�262.
Sustained submicromolar H2O2 levels induce hepcidin via signal transducer and activator of transcription 3 (STAT3). Millonig G et al. J Biol Chem. 2012;287(44):37472�37482.
Sensitive and non-invasive assessment of hepatocellular iron using a novel room-temperature susceptometer. Mueller J et al. J Hepatol. 2017;67(3):535�542.
Novel insights into alcoholic liver disease: iron overload, iron sensing and hemolysis. Mueller S et al. J Transl Int Med. 2022;10(2):92�124.
Direct ingestion of oxidized red blood cells (efferocytosis) by hepatocytes. Zheng C et al. Hepat Med. 2024;16:65�77.
Evidence for alcohol-mediated hemolysis and erythrophagocytosis. Zheng C et al. Redox Biol. 2025;85:103742.
Phosphatidylserine-dependent clearance of damaged red blood cells by liver sinusoidal endothelial cells in alcohol-related liver disease. Li S et al. Biology (Basel). 2026;15(9):699.

Further information

For additional background, technical details and original research data on non-invasive hepatic iron measurement, please visit my dedicated Susceptometry Homepage.