Elucidation Of The Functional Role Of Pcbp-The Cytosolic Iron Chaperone Protein Family, In Cellular Iron Homeostasis

ELUCIDATION OF THE FUNCTIONAL ROLE OF PCBP-THE CYTOSOLIC IRONCHAPERONE PROTEIN FAMILY, IN CELLULAR IRON HOMEOSTASISbyPOORNA SUBRAMANIANAugust 2013Advisors: Dr. Timothy Stemmler and Dr. Brian EdwardsMajor: Biochemistry and Molecular BiologyDegree: Doctor of PhilosophyBiological Role of Ferritin Iron is essential for life and often utilized as a cofactor in manyproteins. In humans, iron accumulation causes cirrhosis, arthritis, cardiomyopathy anddiabetes mellitus, and it is associated with increased risk of cancer and heart disease. Incontrast, decreased brain iron content results in permanent neurocognitive and motorimpairment. Intracellular iron content must be maintained within a narrow range to avoid the adverse effects of iron depletion or excess, and this function is performed by the proteinferritin. Ferritins are iron storage proteins that are ubiquitously expressed in animals, plantsand bacteria. They serve both to sequester excess iron taken up by the cell and to releasestored iron to meet the cell’s metabolic needs during iron scarcity. Ferritin’s capacity to storeiron is therefore essential for life. PCBP1 is an iron chaperone for ferritin Our work shows that human Poly r(C)-BindingProtein family are essential for ferritin iron loading. In vivo, depletion of PCBP1 inhibitsferritin loading and increases cytosolic iron pools. In vitro, PCBPs binds iron with an affinitysimilar to other iron chaperones. Based on these data, we believe the PCBPs arefunctional iron chaperones that deliver iron to ferritin, hence promoting maintenance ofcellular iron homeostasis. Our objective was to characterize the molecular details of the