Mechanisms for increased levels of phosphorylation of elongation factor-2 during hibernation in ground squirrels

Previously, eEF-2 phosphorylation has been identified as a reversible mecha nism involved in the inhibition of the elongation phase of translation. In this study, an increased level of phosphorylation of eukaryotic elongation factor-2 (eEF-2) was observed in the brains and livers of hibernating groun d squirrels. In brain and liver from hibernators, eEF-2 kinase activity was increased relative to that of active animals. The activity of protein phos phatase 2A (PP2A), a phosphatase that dephosphorylates eEF-2, was also decr eased in brain and liver from hibernators. This was associated with an incr ease in the level of inhibitor 2 of PP2A (I-2(PP2A)), although there was an increase in the level of the catalytic subunit of PP2A (PP2A/C) in hiberna ting brains and livers. These results indicate that eEF-2 phosphorylation r epresents a specific and previously uncharacterized mechanism for inhibitio n of the elongation phase of protein synthesis during hibernation. Increase d levels of eEF-2 phosphorylation in hibernators appear to be a component o f the regulated shutdown of cellular functions that permits hibernating ani mals to tolerate severe reductions in cerebral blood flow and oxygen delive ry capacity.