The AMPKyl subunit plays an essential role in erythrocyte membrane elasticity, and its genetic inactivation induces splenomegaly and anemia

AMP‐activated protein kinase (AMPK) is an αβγ heterotrimer conserved throughout evolution and important for energy sensing in all eukaryote cells. AMPK controls metabolism and various cellular events in response to both hormones and changes in cellular energy status. The γ subunit senses intracellular energy status through the competitive binding of AMP and ATP. We show here that targeted disruption of the mouse AMPKyl gene ( Prkαg1 ) causes regenerative hemolytic anemia by increasing the sequestration of abnormal erythrocytes. Prkαg1 –/– mice displayed splenomegaly and iron accumulation due to compensatory splenic erythropoiesis and erythrophagocytosis. Moreover’ AMPKyl‐deficient eryth‐rocytes were highly resistant to osmotic hemolysis and poorly deformable in response to increasing shear stress’ consistent with greater membrane rigidity. No change in cytoskeletal protein composition was observed;however’ the phosphorylation level of adducin’ a protein promoting the binding of spectrin to actin’ was higher in AMPKyl‐deficient erythrocytes. Together’ these results demonstrate that AMPKy1 subunit is required for the maintenance of erythrocyte membrane elasticity.—Foretz, M., Hébrard, S., Guihard, S., Leclerc, J., Do Cruzeiro, M., Hamard, G., Niedergang, F., Gaudry, M., Viollet, B. The AMPK γ1 subunit plays an essential role in erythrocyte membrane elasticity’ and its genetic inactivation induces splenomegaly and anemia. FASEB J. 25, 337–347 (2011). www.fasebj.org