title: Catecholamine stress hormones regulate cellular iron homeostasis by a posttranscriptional mechanism mediated by iron regulatory protein: implication in energy homeostasis.
abstract: Adequate availability of iron is important for cellular energy metabolism. Catecholamines such as epinephrine and norepinephrine promote energy expenditure to adapt to conditions that arose due to stress. To restore the energy balance, epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no direct role of epinephrine/norepinephrine in cellular iron homeostasis has been reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal muscle cells by promoting the binding of iron regulatory proteins to iron-responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H transcripts. Increased transferrin receptor-1, decreased ferritin-H, and increased iron-responsive element-iron regulatory protein interaction are also observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice. We demonstrate the role of epinephrine/norepinephrine-induced generation of reactive oxygen species in converting cytosolic aconitase (ACO1) into iron regulatory protein-1 to bind iron-responsive elements present in UTRs of transferrin receptor-1 and ferritin-H. Our study further reveals that mitochondrial iron content and mitochondrial aconitase (ACO2) activity are elevated by epinephrine/norepinephrine that are blocked by the antioxidant N-acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of reactive oxygen species and iron regulatory protein-1 in this mechanism. This study reveals epinephrine and norepinephrine as novel regulators of cellular iron homeostasis.
authors.affiliation: From the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110 067, India.
authors.forename: Nisha
authors.initials: N
authors.lastname: Tapryal
authors.affiliation: From the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110 067, India.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Vivek G
authors.affiliation: From the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110 067, India ckm2300@mail.jnu.ac.in.
authors.forename: Chinmay K
authors.initials: CK
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional
chemical_list: D002395:Catecholamines; D017931:DNA Primers; D035925:Iron-Regulatory Proteins; D007501:Iron
keywords: Catecholamine; Ferritin; Gene Regulation; Iron Metabolism; Mitochondria; Reactive Oxygen Species (ROS); Transferrin Receptor