AUTHOR=Xu Ying , Yu Zhangjie , Liu Hanxuan , Bian Xiaohan , Tang Weiliang 

TITLE=Erythrocytes enhance oxygen-carrying capacity through self-regulation

JOURNAL=Frontiers in Physiology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1592176

DOI=10.3389/fphys.2025.1592176

ISSN=1664-042X

ABSTRACT=Once considered passive carriers of oxygen, erythrocytes are now understood to play active roles in regulating oxygen homeostasis and redox balance. This review examines the molecular mechanisms through which red blood cells adapt to hypoxic conditions, including nitric oxide (NO)-driven changes in membrane properties, βCys93-dependent S-nitrosylation, adenosine-induced activation of glycolysis, and the development of hypoxic memory via eENT1 degradation. Enzymes such as RBC eNOS, CYB5R3, and G6PD are essential for maintaining NO availability and redox balance by controlling redox state and NADPH synthesis. In addition to their role in gas transport, erythrocytes contribute to intercellular communication, retain organelle remnants under pathological conditions, and are being explored as platforms for drug delivery. Progress in nanotechnology and gene editing has expanded their clinical applications. These findings present erythrocytes as adaptable, multifunctional cells that connect cellular metabolism, vascular biology, and translational research.