Proteasome activity maintains red blood cell integrity during storage and restoration

Researchers examined red blood cells in vitro to determine how proteasome inhibition affects cell quality during storage and physiological restoration. Using the inhibitor epoxomicin, the team tracked cellular alterations during storage and compared young and old red blood cell subpopulations. Proteasome inhibition during storage depleted ATP and altered cell morphology without causing immediate oxidative damage. When returned to physiological conditions, the inhibited cells suffered accelerated ATP loss, extensive protein aggregation, reduced deformability, hemolysis, and increased phosphatidylserine exposure. These detrimental effects were especially severe in long-stored cells. Red blood cells aged in vivo also displayed low proteasomal activity and responded similarly upon physiological restoration, showing that proteasome decline drives features of red blood cell senescence.