Regulatory mechanisms of iron metabolism and their biological impact

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Title Regulatory mechanisms of iron metabolism and their biological impact
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Anderson, Cole Parker
Date 2016-12
Description Iron is a critical micronutrient required for nearly all organisms to live. It is an important cofactor in proteins involved in DNA replication, cellular energy production, and oxygen transport. Nonphysiological levels of iron have pathological consequences ranging from iron deficiency that affects billions worldwide, to the iron overload disorder Hereditary Hemochromatosis that causes debilitating organ failure. Considering the dual nature of iron in healthy and diseased states, organisms have evolved elegant mechanisms to regulate iron homeostasis. This thesis examines the cellular mechanisms involved in controlling cellular iron uptake and storage, and highlights the importance of iron in the innate immune response and endocrine function of the mammalian pancreas. Using C. elegans as a model to study iron metabolism, we show that the nuclear receptor, NHR-14, is a potent repressor of intestinal iron uptake through the iron importer SMF-3. In addition to iron import, NHR-14 regulates a transcriptional response to bacterial infection that is dependent upon the insulin/IGF-1-like signaling (IIS) pathway transcription factor PQM-1. In mammals, cellular iron is maintained by the Iron Regulatory Proteins (IRPs). Mice lacking Iron Regulatory Protein 2 (IRP2) were shown to develop fasting hyperglycemia as a result of defective insulin biosynthesis that likely stems from mitochondrial dysfunction and Endoplasmic Reticulum (ER) stress.
Type Text
Publisher University of Utah
Subject Iron, dietary
Subject MESH Iron, Dietary; Micronutrients; Iron-Regulatory Proteins; Iron Regulatory Protein 1; Iron Regulatory Protein 2; Immunity, Innate; Endoplasmic Reticulum Stress; Pancreas; Caenorhabditis elegans; Caenorhabditis elegans Proteins
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Regulatory Mechanisms of Iron Metabolism and Their Biological Impact
Rights Management Copyright © Cole Parker Anderson 2016
Format application/pdf
Format Medium application/pdf
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6f234qf
Setname ir_etd
ID 1356660
Reference URL https://collections.lib.utah.edu/ark:/87278/s6f234qf
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