Protein Phosphatase 2A Has Positive and Negative Roles in Autophagy

Autophagy is a ubiquitous, homeostatic process involving lysosomal-dependent recycling of intracellular macromolecules and organelles targeted by multi-lamellar vesicles. This multistep process involves a large network of molecules tightly regulated by post-translational mechanisms, including phosphorylation. One critical regulator of this pathway is protein phosphatase 2A (PP2A). Although referred to as a single enzymatic activity, PP2A encompasses multiple serine/threonine phosphatase enzyme complexes formed through the combination of a family of regulatory and scaffolding subunits with a common catalytic subunit. PP2A activity regulates autophagy at multiple checkpoints and can have both stimulatory and inhibitory effects on this process. The final outcome of PP2A activity on autophagic responses is dependent on multiple factors, which include the specific PP2A enzyme activated, cell type, and the nature of autophagic trigger. Alterations in autophagy are increasingly associated with chronic diseases. Therefore, understanding the molecular mechanisms controlling this process may have important implications for designing therapies targeting autophagy.