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Updated: Feb 27, 2026
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Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
Published on: November 26, 2017
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Ageing and hypoxia cause protein aggregation in mitochondria
Daniel M Kaufman1,2, Xia Wu3, Barbara A Scott1
1Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA.
Cell Death and Differentiation
|June 24, 2017
Summary
Hypoxia and aging cause mitochondrial protein aggregation in C. elegans. The mitochondrial unfolded protein response (UPRmt) regulates this aggregation, potentially protecting cells from hypoxic injury.
Area of Science:
- Cell Biology
- Molecular Biology
- Aging Research
Background:
- Cytosolic protein aggregation is linked to aging and neurodegenerative diseases.
- Previous work suggested hypoxia induces protein misfolding and aggregates in mitochondria.
Purpose of the Study:
- To determine if mitochondrial proteins aggregate after hypoxia and other cellular stresses.
- To investigate the role of the mitochondrial unfolded protein response (UPRmt) in regulating mitochondrial protein aggregation.
Main Methods:
- Proteomics analysis of purified C. elegans mitochondria to identify insoluble proteins.
- Utilized GFP-tagged mitochondrial proteins to visualize aggregation.
- Investigated the effect of ATFS-1 (UPRmt regulator) mutants and RNAi on aggregate formation.
Main Results:
- Identified 110 insoluble mitochondrial proteins under normal conditions and 65 after hypoxia.
- Confirmed hypoxia-induced mitochondrial protein aggregation using GFP-tagged proteins.
- Demonstrated that ATFS-1 regulates the number of hypoxia-induced aggregates, with loss-of-function reducing and gain-of-function increasing aggregates.
- Observed protein aggregation during aging.
Conclusions:
- Mitochondrial protein aggregation occurs in response to hypoxic injury and aging in C. elegans.
- The UPRmt, regulated by ATFS-1, plays a role in managing mitochondrial protein aggregation.
- Promoting aggregation of misfolded proteins may be a protective mechanism against hypoxia.
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