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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.adh9215 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Therapeutic Potential of Carbon Dots Derived from Phytochemicals as Nanozymes Exhibiting Superoxide Dismutase Activity for Anemia.
ACS Appl Mater Interfaces
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Anemia is a potentially life-threatening blood disorder caused by an insufficient erythroblast volume in the circulatory system. Self-renewal failure of erythroblast progenitors is one of the key pathological factors leading to erythroblast deficiency. However, there are currently no effective drugs that selectively target this process.
View Article and Find Full Text PDFDonkey-Hide Gelatin-Derived Carbon Dots Activate Erythropoiesis and Eliminate Oxidative Stress for Aplastic Anemia Treatment.
ACS Nano
January 2025
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China.
Article Synopsis
- Aplastic anemia (AA) is a serious blood condition with few treatment options, characterized by halted blood cell production and increased cell death due to oxidative stress.
- Researchers discovered unique carbon dots derived from donkey-hide gelatin (G-CDs) that can stimulate blood cell production and reduce oxidative stress, effectively promoting the recovery of blood cells in AA.
- Administered to AA mice after chemotherapy, G-CDs significantly increased red blood cell levels and improved overall blood function more effectively than the current treatment, erythropoietin (EPO), without negative side effects.
Pediatric Myeloid Neoplasms With UBTF Tandem Duplications: Morphologic, Immunophenotypic, and Clinical Characterization.
Am J Surg Pathol
January 2025
Department of Pathology, St. Jude Children's Research Hospital.
Article Synopsis
- Tandem duplications (TDs) in the UBTF gene are a recently identified genetic alteration linked to pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), establishing UBTF-TD as a distinct subtype of AML.
- A study of 27 pediatric patients revealed that UBTF-TD is commonly associated with symptoms like cytopenia and characteristic changes in bone marrow, such as erythroid hyperplasia and trilineage dysplasia.
- The findings suggest that patients with MDS and AML exhibiting UBTF-TD have similar prognoses, indicating that both conditions may represent different manifestations of the same underlying disease.
Tris(2-chloroethyl) Phosphate Leads to Unbalanced Circulating Erythrocyte in Mice by Activating both Medullary and Extramedullary Erythropoiesis.
Environ Sci Technol
January 2025
Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China.
Tris(2-chloroethyl) phosphate (TCEP), a prevalent organophosphorus flame retardant, has been identified in various environmental matrices and human blood samples, provoking alarm regarding its hematological toxicity, a subject that has not been thoroughly investigated. Red blood cells (RBCs), or erythrocytes, are the predominant cell type in peripheral blood and are crucial for the maintenance of physiological health. This investigation employed oral gavage to examine the effects of TCEP exposure on erythrocyte counts in mice and to clarify the underlying mechanisms.
View Article and Find Full Text PDFAccumulation of free α-globin is a critical factor in the pathogenesis of β-thalassemia. Autophagy plays a crucial role in clearing toxic free α-globin, thereby reducing disease severity. However, the impact of natural mutations in autophagy-related genes (ATGs) on the phenotypic variability of β-thalassemia remains unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!