RBC Metabolism, Pyruvate Kinase Activation and Metabolomics - Emerging Frontiers

Red blood cells (RBCs) are unique in their physiology and morphology and play a central role in circulation. Despite lacking intracellular organelles, they remain metabolically active for approximately 120 days, maintaining hemoglobin function, membrane deformability, and redox homeostasis through specialized metabolic pathways. Their core metabolome includes the Embden–Meyerhof pathway, pentose phosphate pathway (PPP), Rapoport–Luebering shunt, and antioxidant redox systems, which undergo dynamic changes during erythrocyte maturation. Recent advances in RBC metabolomics have greatly improved our understanding of erythrocyte physiology, enzyme-related disorders, and transfusion medicine.Alterations in erythrocyte metabolism contribute to several inherited and acquired disorders. Hemoglobinopathies, including sickle cell disease, thalassemia, and hemoglobin variants such as HbC and HbE, together with glucose-6-phosphate dehydrogenase (G6PD) deficiency, impair RBC function and survival. Post-transcriptional regulation involving mRNA stability, RNA modifications, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the RNA-induced silencing complex (RISC) has also emerged as an important mechanism for maintaining erythrocyte homeostasis and regulating cellular responses.RBCs also play an important role in metabolic disorders, particularly diabetes mellitus. Higher erythrocyte osmotic fragility contributes to hemolysis and anemia, while glycated hemoglobin (HbA1c) serves as a reliable marker of long-term glycemic control. G6PD, the rate-limiting enzyme of the PPP, generates NADPH to maintain reduced glutathione (GSH) and protect RBCs against oxidative stress. In diabetes, chronic hyperglycemia increases reactive oxygen species (ROS), reducing G6PD activity and impairing membrane stability, thereby increasing osmotic fragility and promoting premature hemolysis. Emerging evidence further suggests that miRNA- and RISC-mediated regulatory networks modulate erythrocyte responses to oxidative stress, linking metabolic pathways with post-transcriptional gene regulation.Together, advances in RBC metabolomics and enzyme-targeted therapies continue to expand our understanding of erythrocyte physiology, providing new opportunities for diagnosing and treating hematological and metabolic diseases. This collection aims to bring together biochemical, mechanistic, physiological, translational, clinical, and computational studies, giving researchers and clinicians transdisciplinary visibility and translational relevance, and contributing to developments in transfusion practice, drug development, and diagnostics.The Research Topic will focus on these various aspects of RBC metabolism, enzyme-related disorders, and translational applications, including but not limited to: • Pyruvate kinase activation and other enzyme-targeted mechanisms in RBC metabolism • The role of miRNAs, lncRNAs, and RISC-mediated post-transcriptional regulation in erythrocyte homeostasis • Hemoglobinopathies, including sickle cell disease, thalassemia, and hemoglobin variants • RBC metabolic alterations in diabetes mellitus and other metabolic disorders • Novel methodological and computational approaches to RBC metabolomics Topic editors: Prasanna K. Santhekadur, Vani Rajashekaraiah Source: https://www.frontiersin.org/research-topics/85100/rbc-metabolism-pyruvate-kinase-activation-and-metabolomics---emerging-frontiers