Research Article

NUFIP1 is a ribosome receptor for starvation-induced ribophagy

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Science  18 May 2018:
Vol. 360, Issue 6390, pp. 751-758
DOI: 10.1126/science.aar2663

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A selective autophagy receptor identified

Autophagosomes engulf and degrade cellular components in lysosomes. Degradation of ribosomes is called ribophagy and is an important source of nutrients. Using a recently reported method to isolate lysosomes, Wyant et al. profiled the dynamics of the lysosomal proteome under different nutrient conditions (see the Perspective by Nofal and Rabinowitz). The protein NUFIP1 is an autophagy receptor for ribosomes during starvation-induced ribophagy. NUFIP1 shuttles out of the nucleus and targets its ribosome cargo directly by binding to an autophagosome protein. Loss of NUFIP1 means failure to provide sufficient nucleotides during starvation and, therefore, loss of cells under low nutrient conditions.

Science, this issue p. 751; see also p. 710

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.

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