Phosphorylation of phosphoglucomutase 1 on a peripheral site tunes its activity to regulate glycogen metabolism

Abstract

AbstractRegulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated at a peripheral residue (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans.Significance statementIn this study, we identified phosphoglucomutase 1 (PGM1) as a central metabolic valve that regulates the utilization of the glycogen reserves. We showed that post-translational modification of PGM1 via phosphorylation at a peripheral residue is a key, evolutionary-conserved regulatory mechanism that controls PGM1 activity and the mobilization of the glycogen stores.