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Updated: Aug 5, 2026
09:18
Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
Published on: September 7, 2021
Trr1 (thioredoxin reductase 1) modulates ERphagy in aging via liquid-liquid phase separation
Yuan Gao1, Jingyi Zhao1, Xiangdong Hu1
1Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Autophagy
|July 31, 2026
Summary
Thioredoxin reductase 1 (Trr1) forms dynamic condensates during yeast aging, mitigating endoplasmic reticulum stress and promoting autophagy. Maintaining these liquid-like condensates is crucial for cellular fitness and healthy aging.
Area of Science:
- Cellular Biology
- Aging Research
- Biochemistry
Background:
- Aging leads to impaired autophagy and disrupted proteostasis.
- Liquid-liquid phase separation (LLPS) forms biomolecular condensates with specific functions.
- Thioredoxin reductase 1 (Trr1) is vital for antioxidant defense, and its deletion impairs autophagy.
Purpose of the Study:
- To investigate the role of Trr1's liquid-liquid phase separation (LLPS) in autophagy during aging.
- To understand the mechanism by which Trr1 influences autophagy and cellular fitness.
Main Methods:
- Yeast models of replicative aging.
- Observation of Trr1's phase separation using microscopy.
- Analysis of Trr1 condensate formation in response to ER stress and oxidative stress.
- Assessment of Trr1's role in endoplasmic reticulophagy and Atg8 lipidation.
- Evaluation of cellular fitness linked to Trr1 condensate dynamics.
Main Results:
- Trr1 forms dynamic LLPS condensates during yeast replicative aging.
- Trr1 phase separation is triggered by aging-associated endoplasmic reticulum (ER) stress, not oxidative stress.
- Trr1 condensates are involved in endoplasmic reticulophagy and promote autophagosome development by influencing Atg8 lipidation.
- The liquid-like nature of Trr1 condensates is essential for cellular fitness.
Conclusions:
- Trr1 plays an unconventional role in aging through LLPS.
- Phase-separated Trr1 condensates help mitigate aging-related ER stress, offering insights into healthy aging mechanisms.
- Trr1 condensates represent a potential target for interventions against aging and associated diseases.
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