Beyond ATP: Metabolite Networks as Regulators of Physiological and Pathological Erythroid Differentiation DOI

Axel Joly,

Arthur Schott,

Ira Phadke

et al.

Physiology, Journal Year: 2024, Volume and Issue: 40(1), P. 88 - 101

Published: Sept. 3, 2024

Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls switch HSCs from state to more differentiated state, but it is only recently we have appreciated importance pathways in regulating commitment progenitors distinct hematopoietic In context erythroid differentiation, an extensive network metabolites, including amino acids, sugars, nucleotides, fatty vitamins, iron, required red (RBC) maturation. this review, highlight multifaceted roles via which metabolites regulate physiological erythropoiesis as effects perturbations on lineage differentiation. Of note, differentiation process associated with exceptional breadth solute carrier (SLC) metabolite transporter upregulation. Finally, discuss how recent research, revealing critical impact reprogramming diseases disordered ineffective erythropoiesis, created opportunities development novel metabolic-centered therapeutic strategies.

Language: Английский

Are Mitochondria a Potential Target for Treating β-Thalassemia? DOI Open Access
Elena Di Pierro, Valeria Di Stefano,

Margherita Migone De Amicis

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(4), P. 1095 - 1095

Published: Feb. 8, 2025

The inherited genetic disorder β-thalassemia affects the hematopoietic system and is caused by low production or absence of adult hemoglobin (HbA). Ineffective erythropoiesis hallmark pathophysiology characterized an erythropoietin-driven substantial increase in erythroblast proliferation, coupled with late-stage precursor apoptosis, which results levels circulating mature red blood cells (RBCs) chronic anemia. Mitochondrial dysfunction commonly occurs these because increased demand for energy need to manage abnormal chain synthesis. Moreover, several studies have highlighted importance gradual mitochondrial clearance erythroid cell production. This review offers overview role essential cellular processes, particularly those crucial maintaining RBC health function. Additionally, recent evidence regarding contribution severity discussed, along updated insights into indirect mitochondria-targeting treatments, present potential pharmacological targets.

Language: Английский

Citations

0
Evaluated NSUN3 in reticulocytes from HbH-CS disease that reflects cellular stress in erythroblasts DOI Creative Commons
Haodong Liu,

Chunting Peng,

Qisheng Su

et al.

Annals of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Hemoglobin H Disease-Constant Spring (HbH-CS) represents a severe variant of α-thalassemia characterized by fundamental pathological mechanism involving inadequate synthesis α-globin chains. This deficiency results in the formation unstable (HbH) due to aggregation free β-globin chains, which subsequently induces an imbalance oxidative stress within erythrocytes. leads abnormal accumulation reactive oxygen species (ROS), turn promotes lipid peroxidation, culminating production malondialdehyde (MDA) and significant depletion glutathione (GSH). Concurrently, Nrf2 is translocated nucleus, where it activates antioxidant response element (ARE) mitigate cellular stress. Here, we report that NSUN3 (which, together with ALKBH1, maintains mitochondrial function through m5C→f5C modification) abnormally overexpressed reticulocytes from patients HbH-CS, vitro model overexpression/silencing was constructed using K562 cells, have potential for erythroid lineage differentiation retain intact cluster bead protein genes. Functional assays indicated overexpression significantly intensified intracellular ROS MDA, led reduction GSH levels, diminished overall capacity (T-AOC). may be resulting inhibition respiratory chain complex I, II, IV aberrant modification. In addition, further exacerbates inhibiting phosphorylation hindering its translocation into nucleus weakening system. Moreover, also observed exacerbated DNA damage inhibited value-added activity, silencing showed opposite result. Our research offers initial insights molecular mechanisms modulates erythrocytes via role epigenetic modifications. These findings contribute deeper understanding clinical management Hb H-CS.

Language: Английский

Citations

0
Integrative analysis of copper dysregulation and cuproptosis in postnatal hematopoiesis DOI Creative Commons
Liyun Chen, Qian Wu, Chaohui Lin

et al.

Science Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Beyond ATP: Metabolite Networks as Regulators of Physiological and Pathological Erythroid Differentiation DOI

Axel Joly,

Arthur Schott,

Ira Phadke

et al.

Physiology, Journal Year: 2024, Volume and Issue: 40(1), P. 88 - 101

Published: Sept. 3, 2024

Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls switch HSCs from state to more differentiated state, but it is only recently we have appreciated importance pathways in regulating commitment progenitors distinct hematopoietic In context erythroid differentiation, an extensive network metabolites, including amino acids, sugars, nucleotides, fatty vitamins, iron, required red (RBC) maturation. this review, highlight multifaceted roles via which metabolites regulate physiological erythropoiesis as effects perturbations on lineage differentiation. Of note, differentiation process associated with exceptional breadth solute carrier (SLC) metabolite transporter upregulation. Finally, discuss how recent research, revealing critical impact reprogramming diseases disordered ineffective erythropoiesis, created opportunities development novel metabolic-centered therapeutic strategies.

Language: Английский

Citations

0