Nuclear ESCRT is involved in intranuclear protein quality control by micronucleophagy

Abstract

Intranuclear protein quality control (PQC) is critical for protein homeostasis (or proteostasis) in non-dividing cells including brain nerve cells, but its molecular mechanism remains unresolved. In nutrient-starved conditions, elimination of nucleolar proteins is critical for cell viability in budding yeast, providing a model system to study the mechanisms involved in intranuclear PQC. The nuclear-specific endosomal sorting complex required for transport (ESCRT) CHMP7/Chm7 is linked to neurodegenerative diseases, but its known role is limited. Here, we show a novel role of nuclear ESCRT in intranuclear PQC. Chm7 and its recruiter protein Heh1 were critical for micronucleophagic degradation of nucleolar proteins and for rDNA condensation and nucleolar remodeling, which is prerequisite for proper micronucleophagic degradation of nucleolar proteins. By contrast, Chm7 was dispensable for macronucleophagy. Finally, not only authentic ESCRT but also Chm7 was crucial for the survival of quiescent cells in prolonged nutrient-starved conditions. This study uncovered that nuclear ESCRT together with authentic ESCRT orchestrate micronucleophagic degradation of nucleolar proteins, contributing to intranuclear protein homeostasis.

Keywords: Autophagy; Chm7; ESCRT; Nucleophagy; Protein quality control; TORC1.