| Literature DB >> 35994670 |
Phoenix Toboz1, Mehdi Amiri2,3, Negar Tabatabaei1, Catherine R Dufour3, Seung Hyeon Kim1, Carine Fillebeen4, Charles E Ayemoba1, Arkady Khoutorsky5, Manfred Nairz6, Lijian Shao1, Kostandin V Pajcini1, Ki-Wook Kim1, Vincent Giguère2,3, Regiana L Oliveira7, Marco Constante8, Manuela M Santos8, Carlos R Morales7, Kostas Pantopoulos4, Nahum Sonenberg2,3, Sandra Pinho1, Soroush Tahmasebi1.
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.Entities:
Keywords: GCN2; RBC; hemolytic stress; mRNA translation; macrophages
Mesh：
Substances：
Year: 2022 PMID： 35994670 PMCID： PMC9436309 DOI： 10.1073/pnas.2121251119
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779