Transferrin receptor 1 is a cellular receptor for human heme-albumin
Jennifer Brell, Verena Berg, Madhura Modak, Alexander Puck, Maria Seyerl‐Jiresch, Sarojinidevi Künig, Gerhard J. Zlabinger, Peter Steinberger, Janet Chou, Raif S. Geha, Leopold Öhler, Akihiro Yachie, Hyeryun Choe, Markus Kraller, Hannes Stockinger, Johannes Stöckl
Abstract
Iron is essential for living cells. Uptake of iron-loaded transferrin by the transferrin receptor 1 (CD71, TFR) is a major but not sufficient mechanism and an alternative iron-loaded ligand for CD71 has been assumed. Here, we demonstrate that CD71 utilizes heme-albumin as cargo to transport iron into human cells. Binding and endocytosis of heme-albumin via CD71 was sufficient to promote proliferation of various cell types in the absence of transferrin. Growth and differentiation of cells induced by heme-albumin was dependent on heme-oxygenase 1 (HO-1) function and was accompanied with an increase of the intracellular labile iron pool (LIP). Import of heme-albumin via CD71 was further found to contribute to the efficacy of albumin-based drugs such as the chemotherapeutic Abraxane. Thus, heme-albumin/CD71 interaction is a novel route to transport nutrients or drugs into cells and adds to the emerging function of CD71 as a scavenger receptor.