The red blood cell proteome and interactome identify a Band 3-BLVRB axis regulating hypoxic metabolic adaptation.

The Band 3-BLVRB interaction acts as an oxygen-sensitive switch regulating red blood cell metabolism, with hypoxia causing dissociation and metabolic remodeling.

• Why it matters: Understanding how red blood cells adapt metabolically to oxygen tension is crucial for insights into hypoxic stress, high-altitude adaptation, and related diseases, yet their regulation mechanisms remain unclear.
• What they did: The study used ultrapure human RBCs to map the proteome and oxygen-dependent interactome, identifying a reversible Band 3-BLVRB complex that responds to oxygen levels and influences glycolysis and redox processes.
• The result: Disruption of this axis impairs hypoxic metabolic responses and exercise capacity in mice, highlighting its role in oxygen delivery and metabolic flexibility, with implications for health and disease management.