How the vacuole ESCRTs its own proteins to their final destination

摘要

Lysosomes are key metabolic organelles that influence nutrient sensing, protein traf- ficking, lipid homeostasis, and catabolic metabolism (1). Because of their many roles, how lysosomes receive and degrade proteins has been a pervasive question in cell biology, and has driven the discovery of multiple trafficking pathways that deliver proteins from different regions of the cell to the lysosome for turnover. In budding yeast, the vacuole (functionally equivalent to the lysosome) is a superb model to dissect the mechanisms of endolysosomal trafficking. However, how the vacuole/lysosome senses and degrades its own resident proteins has remained mysterious. This is a critical question, since the vacuole/lysosome surface is home to many nutrient and lipid transporters, which must be selectively maintained or degraded in response metabolic cues to enable cell homeostasis.