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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.
Afiliação
  • Toboz P; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Amiri M; Department of Biochemistry, McGill University, Montreal, QC, H3A 1A3, Canada.
  • Tabatabaei N; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3A 1A3, Canada.
  • Dufour CR; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Kim SH; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3A 1A3, Canada.
  • Fillebeen C; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Ayemoba CE; Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • Khoutorsky A; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Nairz M; Department of Anesthesia and Faculty of Dentistry, McGill University, Montreal, QC, H3A 0G1, Canada.
  • Shao L; Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, 6020, Austria.
  • Pajcini KV; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Kim KW; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Giguère V; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612.
  • Oliveira RL; Department of Biochemistry, McGill University, Montreal, QC, H3A 1A3, Canada.
  • Constante M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, H3A 1A3, Canada.
  • Santos MM; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3G 1Y6, Canada.
  • Morales CR; Nutrition and Microbiome Laboratory, Centre de recherche du CHUM and Department of Medicine, Université de Montréal, Montréal, QC, H3X 0A9, Canada.
  • Pantopoulos K; Nutrition and Microbiome Laboratory, Centre de recherche du CHUM and Department of Medicine, Université de Montréal, Montréal, QC, H3X 0A9, Canada.
  • Sonenberg N; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3G 1Y6, Canada.
  • Pinho S; Lady Davis Institute for Medical Research, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • Tahmasebi S; Department of Biochemistry, McGill University, Montreal, QC, H3A 1A3, Canada.
Proc Natl Acad Sci U S A ; 119(35): e2121251119, 2022 08 30.
Article em En | MEDLINE | ID: mdl-35994670
ABSTRACT
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Eritrócitos / Aminoácidos / Ferro / Fígado / Macrófagos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Eritrócitos / Aminoácidos / Ferro / Fígado / Macrófagos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2022 Tipo de documento: Article