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Updated: Feb 8, 2026

Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
CLIP and cohibin separate rDNA from nucleolar proteins destined for degradation by nucleophagy
Md Golam Mostofa1, Muhammad Arifur Rahman1, Naoki Koike1
1Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan.
Abstract:
Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites proximal to the nuclear-vacuolar junction (NVJ), where micronucleophagy (or piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from nucleolar proteins and moves to sites distal to NVJs. CLIP and cohibin, which tether rDNA to the inner nuclear membrane, were required for repositioning of nucleolar proteins and rDNA, as well as effective nucleophagic degradation of the nucleolar proteins. Furthermore, micronucleophagy itself was necessary for the repositioning of rDNA and nucleolar proteins. However, rDNA escaped from nucleophagic degradation in CLIP- or cohibin-deficient cells. This study reveals that rDNA-nucleolar protein separation is important for the nucleophagic degradation of nucleolar proteins.
Insights
Nutrient starvation triggers nucleophagy in yeast, degrading nucleolar proteins but not DNA. This study reveals that separating ribosomal DNA from proteins is crucial for effective nucleophagy.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Nutrient starvation or TORC1 inactivation induces nucleophagy, a selective autophagy targeting nucleolar components in budding yeast.
- Ribosomal DNA (rDNA), despite being in the nucleolus, is resistant to nucleophagy.
Purpose of the Study:
- To investigate the mechanisms behind the selective degradation of nucleolar components during nucleophagy.
- To understand the fate of rDNA during nutrient starvation-induced nucleophagy.
Main Methods:
- Yeast genetics and microscopy techniques.
- Analysis of protein and DNA localization.
- Investigating the role of CLIP and cohibin in nucleophagy.
Main Results:
- TORC1 inactivation causes nucleolar proteins and rDNA to relocate to distinct cellular sites.
- Nucleolar proteins move towards the nuclear-vacuolar junction (NVJ) for potential degradation via micronucleophagy.
- rDNA dissociates from nucleolar proteins and moves away from NVJs.
- CLIP and cohibin are essential for the repositioning of nucleolar proteins and rDNA, and for efficient nucleophagic degradation.
- Micronucleophagy is necessary for the repositioning of rDNA and nucleolar proteins.
Conclusions:
- Separation of rDNA from nucleolar proteins is a critical step for the selective degradation of nucleolar components during nucleophagy.
- CLIP and cohibin play key roles in orchestrating this separation and subsequent degradation process.
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