NCOA4 Deficiency Impairs Systemic Iron Homeostasis

Cell Reports
Roberto BellelliFrancesca Carlomagno

Abstract

The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2-3 mg/kg), mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg), mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239-614) restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

References

May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Yeh, C Chang
Jan 5, 2005·Toxicology and Applied Pharmacology·G Papanikolaou, K Pantopoulos
Apr 14, 2005·Blood·Gerhard J WeberLeonard I Zon
Apr 11, 2006·Nature Genetics·Jodie L BabittHerbert Y Lin
Oct 4, 2006·Annual Review of Physiology·Nancy C Andrews, Paul J Schmidt
Oct 22, 2008·Biochimica Et Biophysica Acta·Paolo ArosioPatrizia Cavadini
Dec 22, 2009·Nature Cell Biology·Simon Bekker-JensenNiels Mailand
Jul 7, 2010·Cell·Matthias W HentzeClara Camaschella
Sep 8, 2010·Cell Metabolism·Liviu VanoaicaLukas C Kühn
Jan 27, 2012·The New England Journal of Medicine·Robert E Fleming, Prem Ponka
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Tomas Ganz, Elizabeta Nemeth
Sep 6, 2012·Autophagy·David ColecchiaMario Chiariello
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Jun 1, 2013·The Journal of Clinical Investigation·Ningning ZhaoCaroline A Enns
Jun 10, 2014·Molecular Cell·Roberto BellelliFrancesca Carlomagno
Jul 2, 2014·Frontiers in Pharmacology·De-Liang ZhangTracey A Rouault
Dec 17, 2014·Blood·Antonella NaiClara Camaschella
Feb 25, 2015·Current Opinion in Hematology·Airie Kim, Elizabeta Nemeth

❮ Previous
Next ❯

Citations

Mar 10, 2016·Journal of Molecular Biology·Joseph D Mancias, Alec C Kimmelman
Aug 16, 2016·Cell Research·Minghui GaoXuejun Jiang
Nov 5, 2016·Biochimica Et Biophysica Acta·Amel HamdiPrem Ponka
Mar 30, 2017·IUBMB Life·Paolo ArosioMaura Poli
Apr 5, 2017·The Journal of Clinical Investigation·Moon-Suhn RyuCaroline C Philpott
Apr 8, 2017·IUBMB Life·George Papanikolaou, Kostas Pantopoulos
Jul 4, 2017·Metallomics : Integrated Biometal Science·Elena GammellaStefania Recalcati
Jun 28, 2017·Molecular and Cellular Endocrinology·Roberto BellelliMassimo Santoro
Feb 21, 2018·Current Opinion in Hematology·Caroline C Philpott
Aug 11, 2017·Antioxidants & Redox Signaling·Alessandro MatteLucia De Franceschi
May 24, 2018·International Journal of Molecular Sciences·Liangfu ZhouPeng Shang
Nov 29, 2017·Experimental & Applied Acarology·Nicole O Moura-MartinianoCarlos Augusto Gomes Soares
Jun 26, 2018·British Journal of Haematology·Clara Camaschella, Alessia Pagani
Jun 21, 2018·Metallomics : Integrated Biometal Science·Huanhuan Lv, Peng Shang
Aug 5, 2018·Journal of Cellular Physiology·Mingzhu TangLinxi Chen
Nov 8, 2018·Blood·Clara Camaschella
Mar 12, 2019·Current Opinion in Hematology·Alessandro Matte, Lucia De Franceschi
Jun 1, 2018·Annual Review of Nutrition·Marianne Wessling-Resnick
Aug 19, 2017·Autophagy·Akiko KumaNoboru Mizushima
Sep 1, 2019·Medicinal Research Reviews·Zhong-Ming Qian, Ya Ke
Jan 18, 2017·Biological Chemistry·Stephanie RockfieldMeera Nanjundan
Aug 9, 2020·Cell Biology International·Mazen HasanNupur K Das
Aug 18, 2020·Autophagy·Xin ChenDaolin Tang
Apr 4, 2017·Médecine sciences : M/S·Ahmed Hamaï, Maryam Mehrpour
Jun 16, 2017·The Journal of Biological Chemistry·Caroline C PhilpottSarju Patel
Oct 27, 2018·Pharmaceuticals·Naiara Santana-Codina, Joseph D Mancias
Dec 14, 2018·International Journal of Molecular Sciences·Po-Yuan Ke
Jul 10, 2019·Annual Review of Cell and Developmental Biology·Hideaki Morishita, Noboru Mizushima
Dec 7, 2019·Hematology·Yelena Z Ginzburg
Jun 21, 2020·Nutrients·Michał WicińskiBartosz Malinowski
Jan 6, 2019·Pharmaceuticals·Joana NevesMartina U Muckenthaler
Dec 12, 2019·Frontiers in Molecular Biosciences·Shane J F CroninJosef M Penninger
Jun 16, 2017·The Journal of Biological Chemistry·Richard Coffey, Tomas Ganz
Mar 16, 2019·Frontiers in Immunology·Rosa SottileEnnio Carbone
Jan 11, 2020·Frontiers in Neuroscience·Barry B Muhoberac, Ruben Vidal
Jan 31, 2020·JCI Insight·Nathan C WinnAlyssa H Hasty
Apr 2, 2019·Frontiers in Neuroscience·Maria Quiles Del Rey, Joseph D Mancias
Sep 19, 2020·American Journal of Hematology·Katarzyna Mleczko-Sanecka, Laura Silvestri
Nov 25, 2020·Antioxidants & Redox Signaling·Sayantani SinhaDelfim Duarte
Jul 2, 2019·Journal of Molecular Biology·Sebastian E Koschade, Christian H Brandts
Sep 22, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fan FengXiujie Wu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms