College of Food, Ag & Nat Res Sci
In humans, suboptimal iron supply causes anemia, impaired motor and cognitive functioning, and many other health defects. On the other hand, free inorganic iron can facilitate the formation of harmful reactive oxygen species, and thus cause organ failure and carcinogenesis when in excess. Hence, cells need to maintain a balance between iron supply and demand by coordinating regulation of proteins involved in iron trafficking, storage, and utilization. While the regulatory mechanisms for changes in cellular iron homeostasis have been extensively studied, how intracellular iron is differentially handled in response to physiological messages remains largely unknown. Recent studies implicate the potential involvement of a selective autophagic cargo receptor for ferritin, NCOA4, in such responses. The central hypothesis of this research is that NCOA4-mediated ferritinophagy respond to physiological cues requiring changes in cytosolic iron handling, and thereby contribute to tissue and whole body iron metabolism. The primary aim of these studies is to elucidate the physiological role of PCBP and NCOA4 proteins in various organs and cell-types, particularly those featuring dynamic changes in the intracellular iron pool or high iron demands. The project will provide the molecular basis of cellular iron regulation and its implications in systemic iron physiology. Furthermore, it is expected to reveal new therapeutic targets and treatment strategies for disorders associated with aberrant tissue iron accumulation or cellular distribution.