NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Abstract

The lysosome degrades and recycles macromolecules, signals to the master growth regulator mTORC1, and is associated with human disease. Here, we performed quantitative proteomic analyses of lysosomes rapidly isolated using the LysoIP method and find that nutrient levels and mTOR dynamically modulate the lysosomal proteome. We focus on NUFIP1, a protein that upon mTORC1 inhibition redistributes from the nucleus to autophagosomes and lysosomes. Upon these conditions, NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to LC3B. The starvation-induced degradation of ribosomes via autophagy (ribophagy) depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival. We propose that NUFIP1 is a receptor for the selective autophagy of ribosomes.