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Significance In this study, we define a regulatory pathway controlling tissue-resident macrophages during stress through the translational control of a subset of messenger RNAs (mRNAs) and transcriptional reprogramming. Our data… Click to show full abstract
Significance In this study, we define a regulatory pathway controlling tissue-resident macrophages during stress through the translational control of a subset of messenger RNAs (mRNAs) and transcriptional reprogramming. Our data reveal that the GCN2-eIF2α pathway is enriched and activated in macrophages. Using mice devoid of GCN2, we show that lack of GCN2 interferes with the clearance of red blood cells (RBCs) during stress. We report an unexpected role of GCN2 in regulating lysosome maturation and phagocytosis of RBCs by macrophages during stress. Thus, we conclude that GCN2 regulates the clearance of RBCs through translational control of ATF4 mRNA in liver macrophages.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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