A glutamine metabolic switch supports erythropoiesis.

Autor:	Lyu J; Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Gu Z; Children's Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Zhang Y; Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Vu HS; Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Lechauve C; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Cai F; Children's Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Cao H; Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Keith J; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Brancaleoni V; Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Granata F; Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Motta I; Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy., Cappellini MD; Unit of Medicine and Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Huang LJ; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., DeBerardinis RJ; Children's Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Weiss MJ; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Ni M; Division of Molecular Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Xu J; Center of Excellence for Leukemia Studies, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2024 Nov 15; Vol. 386 (6723), pp. eadh9215. Date of Electronic Publication: 2024 Nov 15.
DOI:	10.1126/science.adh9215
Abstrakt:	Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.
Databáze:	MEDLINE
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