Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification.

Animals Cell Line, Tumor Glucose Intolerance / genetics Homeostasis Insulin / metabolism Insulin-Secreting Cells / metabolism Insulinoma / genetics Iron / metabolism Iron Regulatory Protein 2 / genetics Iron-Sulfur Proteins / metabolism Mice, Inbred C57BL Mice, Knockout Pancreatic Neoplasms / genetics Proinsulin / genetics RNA, Transfer, Lys / genetics Rats Unfolded Protein Response / genetics tRNA Methyltransferases / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 01 2020
Historique:
received: 03 12 2018
accepted: 06 12 2019
entrez: 17 1 2020
pubmed: 17 1 2020
medline: 14 4 2020
Statut: epublish

Résumé

Regulation of cellular iron homeostasis is crucial as both iron excess and deficiency cause hematological and neurodegenerative diseases. Here we show that mice lacking iron-regulatory protein 2 (Irp2), a regulator of cellular iron homeostasis, develop diabetes. Irp2 post-transcriptionally regulates the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-storage protein ferritin, and dysregulation of these proteins due to Irp2 loss causes functional iron deficiency in β cells. This impairs Fe-S cluster biosynthesis, reducing the function of Cdkal1, an Fe-S cluster enzyme that catalyzes methylthiolation of t

Identifiants

DOI: 10.1038/s41467-019-14004-5 PMID: 31941883 PMC: PMC6962211
pubmed: 31941883
doi: 10.1038/s41467-019-14004-5
pii: 10.1038/s41467-019-14004-5
pmc: PMC6962211
doi:

Substances chimiques

Insulin 0
Iron-Sulfur Proteins 0
RNA, Transfer, Lys 0
Proinsulin 9035-68-1
Iron E1UOL152H7
tRNA Methyltransferases EC 2.1.1.-
CDKAL1 protein, mouse EC 2.8.4.5
Ireb2 protein, mouse EC 4.2.1.3
Iron Regulatory Protein 2 EC 4.2.1.3

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

296

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM045201
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107712
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK110858
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007115
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES002109
Pays : United States

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Auteurs

Maria C Ferreira Dos Santos (MCFD)

Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, UT, 84112, USA.
Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
ORCID: 0000-0003-0231-6538

Cole P Anderson (CP)

Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
Department of Oncological Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
Landstuhl Regional Medical Center, 66849, Landstuhl, Germany.

Susanne Neschen (S)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.

Kimberly B Zumbrennen-Bullough (KB)

Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
Department of Oncological Sciences, University of Utah, Salt Lake City, UT, 84112, USA.

Steven J Romney (SJ)

Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, UT, 84112, USA.
Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
Thermo Fisher Scientific, Waltham, MA, 02451, USA.

Melanie Kahle-Stephan (M)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Medizinische Hochschule Brandenburg Theodor Fontane Institut für Sozialmedizin und Epidemiologie, 14770, Brandenburg an der Havel, Germany.

Birgit Rathkolb (B)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen Strasse 25, 81377, Munich, Germany.
ORCID: 0000-0003-1239-0547

Valerie Gailus-Durner (V)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
ORCID: 0000-0002-6076-0111

Helmut Fuchs (H)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
ORCID: 0000-0002-5143-2677

Eckhard Wolf (E)

Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen Strasse 25, 81377, Munich, Germany.
ORCID: 0000-0002-0430-9510

Jan Rozman (J)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prumyslova, 595, 252 50 Vestec, Czech Republic.
ORCID: 0000-0002-8035-8904

Martin Hrabe de Angelis (MH)

German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, Alte Akademie 8, 85354, Freising, Germany.
ORCID: 0000-0002-7898-2353

Weiling Maggie Cai (WM)

Department of Microbiology, National University of Singapore, Singapore, Singapore, 119077.
Antimicrobial Resistance Interdisciplinary Research Group (IRG), Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, Singapore, 138602.
Agilent Technologies, 1 Yishun Ave 7, Singapore, Singapore, 768923.

Malini Rajan (M)

Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, UT, 84112, USA.
Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA.
ORCID: 0000-0002-7653-4223

Jennifer Hu (J)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Celgene Corporation, 1616 Eastlake Ave East, Seattle, WA, 98102, USA.

Peter C Dedon (PC)

Antimicrobial Resistance Interdisciplinary Research Group (IRG), Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore, Singapore, 138602.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
ORCID: 0000-0003-0011-3067

Elizabeth A Leibold (EA)

Department of Medicine, Division of Hematology, University of Utah, Salt Lake City, UT, 84112, USA. betty.leibold@genetics.utah.edu.
Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA. betty.leibold@genetics.utah.edu.
Department of Oncological Sciences, University of Utah, Salt Lake City, UT, 84112, USA. betty.leibold@genetics.utah.edu.
ORCID: 0000-0003-1000-9503

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Irp2 regulates insulin production through...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Irp2 regulates insulin production through...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme du glucose › Hyperglycémie › Intolérance au glucose › Irp2 regulates insulin production through...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Irp2 regulates insulin production through...
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