title: An essential cell-autonomous role for hepcidin in cardiac iron homeostasis.
abstract: Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Samira
authors.identifier: 0000-0001-7797-1567
authors.initials: S
authors.lastname: Lakhal-Littleton
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Magda
authors.initials: M
authors.lastname: Wolna
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Heather
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Marcella
authors.initials: M
authors.lastname: Brescia
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Vicky
authors.initials: V
authors.lastname: Ball
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Diaz
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Santos
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Biggs
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Benjamin
authors.identifier: 0000-0003-3623-600X
authors.initials: B
authors.lastname: Davies
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Peter A
authors.identifier: 0000-0002-4975-0609
authors.initials: PA
authors.lastname: Robbins
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D000098742:Ferroportin; D007501:Iron
keywords: biochemistry; cell biology; ferroportin; hepcidin; iron; mouse