Sharon Gim
Pronouns: she/her/hers
Research Mentor(s): Yatrik Shah
Research Mentor School/College/Department: Molecular & Integrative Physiology / Medicine
Program: UROP
Session: Session 6 (3:40pm – 4:30pm)
Authors: Sharon Gim, Nupur Das, Yatrik Shah
Abstract
Iron is an essential element for almost all living organisms on earth. It plays a critical role in vital processes including DNA synthesis, oxygen transport and erythropoiesis. Iron homeostasis at both cellular and systemic levels is tightly maintained as both its deficiency and excess are detrimental for health. Cellular iron transport as well as storage mechanisms are regulated in a well-coordinated manner by iron regulatory genes. After uptake into the cell, iron is utilized for cellular processes, and surplus iron is either sent for storage or exported out. Ferritin (Ftn) is the cellular iron storage protein which not only protects the cell from excess iron-mediated toxicity, but also provides iron during conditions of deficiency or high demand. On the other hand, ferroportin 1 (FPN1) is the only known cellular iron exporter that plays a critical role for maintaining cellular iron levels. At the systemic level, FPN1 is negatively regulated by hepatic hormone hepcidin that limits the intestinal iron absorption in mammals. Hepcidin-FPN1 axis is critical for systemic iron balance, and almost every iron disorder is associated with dysregulation of this axis. Nuclear receptor coactivator 4 (NCOA4) acts as a cargo receptor for lysosomal degradation of Ftn by a process known as ferritinophagy. Recently published works using in vitro (in cells) and in vivo (in living organism) models have established that NCOA4-mediated Ftn breakdown is critical for maintaining cellular as well as systemic iron balance. But it is not known if and how the ferritinophagy pathways interact with Fpn1-mediated cellular iron efflux mechanisms. We hypothesize that NCOA4-mediated ferritinophagy cross-talks with the iron efflux mechanisms for cellular iron homeostasis. To address this, we shall use a doxycycline-inducible FPN1 overexpression HEK293 (FPN1-OE) cell line. FPN1-OE cells are amenable to easy manipulation of intracellular iron levels by doxycycline and exogenous hepcidin treatment. We will study FPN1, NCOA4, and Ftn gene expression in this experimental setting using quantitative RT-PCR (qPCR) and Western blot analysis.
