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Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
Published on: December 18, 2013
Single-Cell Proteomics Decodes the Cellular Response to Lysosomal Storage in C. elegans Coelomocytes
Yiming Lei1,2,3, Fanghua Lu4,5, Qinqin Xu5
1School of Life Sciences, Fudan University, Shanghai 200433, China.
International Journal of Molecular Sciences
|May 27, 2026
Summary
Single-cell proteomics reveals how cells cope with lysosomal storage by upregulating nearly 1000 proteins. This response involves endoplasmic reticulum (ER) quality control and the ubiquitin-proteasome system (UPS) to manage cellular stress.
Area of Science:
- Cell Biology
- Proteomics
- Molecular Biology
Background:
- Lysosomal storage diseases involve substrate accumulation, but single-cell proteomic changes are poorly understood.
- Cellular responses to lysosomal stress are not well-defined.
Purpose of the Study:
- To investigate single-cell proteomic remodeling during lysosomal storage.
- To identify cellular coping mechanisms in response to lysosomal stress.
Main Methods:
- Deep-coverage single-cell proteomics was used to analyze C. elegans coelomocytes.
- Proteomic data was analyzed to identify changes in protein expression and cellular pathways.
Main Results:
- Lysosomal storage induced massive, asymmetric upregulation of approximately 1000 proteins.
- A coordinated compensatory response included endoplasmic reticulum (ER) quality control (ER unfolded protein response, ER-associated degradation) and ubiquitin-proteasome system (UPS) hyperactivation.
- Mitochondria showed a discordant response with increased bioenergetics and proteostatic stress.
Conclusions:
- Single-cell proteomics provides a high-resolution blueprint of cellular strategies during lysosomal collapse.
- Cells employ hierarchical compensatory quality control mechanisms to survive lysosomal stress.
- Understanding these mechanisms is crucial for lysosome-related disease research.
