The AMPKγ1 subunit plays an essential role in erythrocyte membrane elasticity, and its genetic inactivation induces splenomegaly and anemia

AMP-activated protein kinase (AMPK) is an alpha beta gamma 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 gamma subunit senses intracellular energy status through the competitive binding of AMP and ATP. We show here that targeted disruption of the mouse AMPK gamma 1 gene (Prkag1) causes regenerative hemolytic anemia by increasing the sequestration of abnormal erythrocytes. Prkag1(-/-) mice displayed splenomegaly and iron accumulation due to compensatory splenic erythropoiesis and erythrophagocytosis. Moreover, AMPK gamma 1-deficient erythrocytes 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 AMPK gamma 1-deficient erythrocytes. Together, these results demonstrate that AMPK gamma 1 subunit is required for the maintenance of erythrocyte membrane elasticity.-Foretz, M., Hebrard, S., Guihard, S., Leclerc, J., Do Cruzeiro, M., Hamard, G., Niedergang, F., Gaudry, M., Viollet, B. The AMPK gamma 1 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