NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Science. 2018 May 18;360(6390):751-758. doi: 10.1126/science.aar2663. Epub 2018 Apr 26.

Abstract

The lysosome degrades and recycles macromolecules, signals to the master growth regulator mTORC1 [mechanistic target of rapamycin (mTOR) complex 1], and is associated with human disease. We performed quantitative proteomic analyses of rapidly isolated lysosomes and found that nutrient levels and mTOR dynamically modulate the lysosomal proteome. Upon mTORC1 inhibition, NUFIP1 (nuclear fragile X mental retardation-interacting protein 1) redistributes from the nucleus to autophagosomes and lysosomes. Upon these conditions, NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to microtubule-associated proteins 1A/1B light chain 3B (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / deficiency*
  • Animals
  • Autophagosomes / metabolism*
  • Autophagy*
  • Cell Nucleus / metabolism
  • HEK293 Cells
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proteome / metabolism
  • Proteomics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Ribosomes / metabolism*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors

Substances

  • Amino Acids
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • NUFIP1 protein, human
  • Nuclear Proteins
  • Proteome
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • ZNHIT3 protein, human
  • ribosome receptor
  • MTOR protein, human
  • TOR Serine-Threonine Kinases