The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importa...

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Autores principales: Toboz, Phoenix, Amiri, Mehdi, Tabatabaei, Negar, Dufour, Catherine R., Kim, Seung Hyeon, Fillebeen, Carine, Ayemoba, Charles E., Khoutorsky, Arkady, Nairz, Manfred, Shao, Lijian, Pajcini, Kostandin V., Kim, Ki-Wook, Giguère, Vincent, Oliveira, Regiana L., Constante, Marco, Santos, Manuela M., Morales, Carlos R., Pantopoulos, Kostas, Sonenberg, Nahum, Pinho, Sandra, Tahmasebi, Soroush
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436309/
https://www.ncbi.nlm.nih.gov/pubmed/35994670
http://dx.doi.org/10.1073/pnas.2121251119
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author Toboz, Phoenix
Amiri, Mehdi
Tabatabaei, Negar
Dufour, Catherine R.
Kim, Seung Hyeon
Fillebeen, Carine
Ayemoba, Charles E.
Khoutorsky, Arkady
Nairz, Manfred
Shao, Lijian
Pajcini, Kostandin V.
Kim, Ki-Wook
Giguère, Vincent
Oliveira, Regiana L.
Constante, Marco
Santos, Manuela M.
Morales, Carlos R.
Pantopoulos, Kostas
Sonenberg, Nahum
Pinho, Sandra
Tahmasebi, Soroush
author_facet Toboz, Phoenix
Amiri, Mehdi
Tabatabaei, Negar
Dufour, Catherine R.
Kim, Seung Hyeon
Fillebeen, Carine
Ayemoba, Charles E.
Khoutorsky, Arkady
Nairz, Manfred
Shao, Lijian
Pajcini, Kostandin V.
Kim, Ki-Wook
Giguère, Vincent
Oliveira, Regiana L.
Constante, Marco
Santos, Manuela M.
Morales, Carlos R.
Pantopoulos, Kostas
Sonenberg, Nahum
Pinho, Sandra
Tahmasebi, Soroush
author_sort Toboz, Phoenix
collection PubMed
description GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout (GCN2(−/−)) mice displayed resistance to anemia compared with wild-type (GCN2(+/+)) mice. GCN2(−/−) liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2(−/−) cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling.
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spelling pubmed-94363092023-02-22 The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages Toboz, Phoenix Amiri, Mehdi Tabatabaei, Negar Dufour, Catherine R. Kim, Seung Hyeon Fillebeen, Carine Ayemoba, Charles E. Khoutorsky, Arkady Nairz, Manfred Shao, Lijian Pajcini, Kostandin V. Kim, Ki-Wook Giguère, Vincent Oliveira, Regiana L. Constante, Marco Santos, Manuela M. Morales, Carlos R. Pantopoulos, Kostas Sonenberg, Nahum Pinho, Sandra Tahmasebi, Soroush Proc Natl Acad Sci U S A Biological Sciences GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout (GCN2(−/−)) mice displayed resistance to anemia compared with wild-type (GCN2(+/+)) mice. GCN2(−/−) liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2(−/−) cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling. National Academy of Sciences 2022-08-22 2022-08-30 /pmc/articles/PMC9436309/ /pubmed/35994670 http://dx.doi.org/10.1073/pnas.2121251119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Toboz, Phoenix
Amiri, Mehdi
Tabatabaei, Negar
Dufour, Catherine R.
Kim, Seung Hyeon
Fillebeen, Carine
Ayemoba, Charles E.
Khoutorsky, Arkady
Nairz, Manfred
Shao, Lijian
Pajcini, Kostandin V.
Kim, Ki-Wook
Giguère, Vincent
Oliveira, Regiana L.
Constante, Marco
Santos, Manuela M.
Morales, Carlos R.
Pantopoulos, Kostas
Sonenberg, Nahum
Pinho, Sandra
Tahmasebi, Soroush
The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title_full The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title_fullStr The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title_full_unstemmed The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title_short The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
title_sort amino acid sensor gcn2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436309/
https://www.ncbi.nlm.nih.gov/pubmed/35994670
http://dx.doi.org/10.1073/pnas.2121251119
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