Format

Send to

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

NUFIP1 is a ribosome receptor for starvation-induced ribophagy.

Wyant GA1,2,3,4, Abu-Remaileh M1,2,3,4, Frenkel EM1,2,3,4, Laqtom NN1,2,3,4, Dharamdasani V1,2,3,4, Lewis CA1, Chan SH1, Heinze I5, Ori A6, Sabatini DM7,2,3,4.

Author information

1
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
2
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
4
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
5
Leibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany.
6
Leibniz Institute on Aging-Fritz Lipmann Institute, 07745 Jena, Germany. sabatini@wi.mit.edu alessandro.ori@leibniz-fli.de.
7
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. sabatini@wi.mit.edu alessandro.ori@leibniz-fli.de.

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.

Comment in

PMID:
29700228
PMCID:
PMC6020066
[Available on 2019-05-18]
DOI:
10.1126/science.aar2663
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center