# Defining the mechanism of starvation-induced ribophagy

> **NIH NIH F31** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $46,036

## Abstract

Project Summary/Abstract:
 The mTORC1 kinase complex is a major regulator of cell growth and metabolism, and is deregulated in
a variety of common human diseases such as diabetes and cancer. In addition, chronic mTOR inhibition
increases lifespan in a variety of model organisms. Many of these disease phenotypes have been attributed to
the role of autophagy downstream of starvation-induced mTORC1 inhibition. Therefore, understanding the
regulation of autophagy by mTORC1 is of great importance to guide future therapeutics and to uncover
fundamental cellular biological processes. Of particular interest to us is the role of autophagy-mediated
degradation of ribosomes in response to nutrient depravation or mTOR inhibition. We reasoned that because
ribosomes make up ~50% and ~80% of the total cellular protein and RNA, that their degradation is likely
important for maintaining cellular homeostasis under starvation conditions. This process of ribosome degradation
via autophagy (ribophagy) is yet to be fully understood. We recently discovered that NUFIP1, a protein whose
nuclear function is associated with snoRNP mediated modification of the ribosome, can act as a selective
autophagy receptor for ribosomes in the cytoplasm. NUFIP1-dependent selective autophagy operates
downstream of the mTORC1 pathway and is induced via nutrient deprivation or with mTOR inhibitors. The goal
of the proposed research is to define the mechanism by which NUFIP1 recognizes ribosomes for
degradation, and how mTORC1 is involved in mediating this signal. To that end we propose the following
aims:
1. Determine the binding site of NUFIP1 on the ribosome.
2. Identify the modification or accessory protein needed for the starvation regulated NUFIP1-ribosome
interaction.
3. Determine how mTORC1 signaling initiates selective ribophagy.
By taking both hypothesis driven and unbiased approaches, the proposed work will define the mechanism of
selective ribophagy in response to starvation. Determining the NUFIP1-ribosome binding site as well as proteins
involved in marking ribosomes for degradation may lead to novel therapies targeting ribosome recycling. This
could have implications for diseases like cancer that co-opt autophagy to maintain their proliferative potential.

## Key facts

- **NIH application ID:** 10174864
- **Project number:** 5F31CA232355-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Justin Michael Roberts
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174864

## Citation

> US National Institutes of Health, RePORTER application 10174864, Defining the mechanism of starvation-induced ribophagy (5F31CA232355-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10174864. Licensed CC0.

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