How the vacuole ESCRTs its own proteins to their final destination

Abstract

Lysosomes (vacuoles in yeast) are master regulators of metabolism and protein turnover, but how they degrade their own resident proteins is unclear. Recently, multiple models have been proposed explaining yeast vacuole protein sorting, but the role of the ESCRT pathway was unclear. In this JCB issue, work from Yang et al. (https://doi.org/10.1083/jcb.202012104) highlights how the ESCRT pathway localizes to the vacuole surface to execute protein sorting of its resident proteins.

Figure 1.

Cartoon schematic of the models for resident vacuole protein turnover. Left: ESCRT-dependent sorting of vacuole proteins via recruitment of ESCRTs to ubiquitinated surface proteins, which are sorted into a vesicle that protrudes into the vacuole lumen and is degraded. Right: ILF pathway showing an ESCRT-independent selective sorting of proteins into a fragment, which via homotypic vacuole fusion is deposited into the vacuole lumen and then degraded.