♦ See referenced article, J. Biol. Chem. 2011, 286, 8308–8324
Autophagy is an evolutionarily preserved catabolic process that involves the degradation of a cell's own proteins and organelles. The tightly regulated process is used to maintain intracellular homeostasis and to contribute to starvation and stress responses. Autophagy can both protect against and promote cell death, depending on the circumstances. Despite the importance of this process, the different autophagy pathways and the cellular context in which they occur remain to be elucidated. In this study, Daniel Grasso and colleagues thoroughly characterized a novel selective autophagy that works as a protective cell response. This new autophagy is activated in pancreatic acinar cells during pancreatitis-induced vesicular transport alteration to sequester and degrade potentially deleterious activated zymogen granules. The scientists coined the term “zymophagy” to refer to this process, which is mediated by the autophagy-related protein VMP1, the ubiquitin-protease USP9x, and the ubiquitin-binding protein p62.
Lamp2 and trypsinogen signals show large lysosomes without trypsinogen (magnification) suggesting that zymogen granules are eventually degraded in the late large autolysosome.