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Updated: Jun 11, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Metacaspase Yca1 is required for clearance of insoluble protein aggregates
Robin E C Lee1, Steve Brunette, Lawrence G Puente
1Ottawa Hospital Research Institute, Sprott Centre for Stem Cell Research, Ottawa Hospital, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8L6.
Abstract:
In complex organisms, caspase proteases mediate a variety of cell behaviors, including proliferation, differentiation, and programmed cell death/apoptosis. Structural homologs to the caspase family (termed metacaspases) engage apoptosis in single-cell eukaryotes, yet the molecular mechanisms that contribute to nondeath roles are currently undefined. Here, we report an unexpected role for the Saccharomyces cerevisiae metacaspase Yca1 in protein quality control. Quantitative proteomic analysis of Deltayca1 cells identified significant alterations to vacuolar catabolism and stress-response proteins in the absence of induced stress. Yca1 protein complexes are enriched for aggregate-remodeling chaperones that colocalize with Yca1-GFP fusions. Finally, deletion and inactivation mutants of Yca1 accrue protein aggregates and autophagic bodies during log-phase growth. Together, our results show that Yca1 contributes to the fitness and adaptability of growing yeast through an aggregate remodeling activity.
Insights
The yeast metacaspase Yca1 unexpectedly manages protein quality control by remodeling aggregates. This function is crucial for yeast fitness and adaptability during growth.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Caspase proteases regulate cell behaviors like apoptosis in complex organisms.
- Metacaspases, structural homologs to caspases, are involved in apoptosis in single-cell eukaryotes.
- The non-death roles of metacaspases remain largely undefined.
Purpose of the Study:
- To investigate the functions of Saccharomyces cerevisiae metacaspase Yca1 beyond apoptosis.
- To explore the role of Yca1 in protein quality control mechanisms.
- To understand how Yca1 contributes to cellular fitness and adaptability.
Main Methods:
- Quantitative proteomic analysis of Deltayca1 yeast cells.
- Co-immunoprecipitation to identify Yca1 interacting proteins.
- Microscopy of Yca1-GFP fusions and Yca1 mutants to observe protein aggregates and autophagic bodies.
Main Results:
- Absence of Yca1 led to altered vacuolar catabolism and stress-response proteins without induced stress.
- Yca1 protein complexes include aggregate-remodeling chaperones and colocalize with Yca1.
- Yca1 deletion and inactivation mutants accumulate protein aggregates and autophagic bodies during growth.
Conclusions:
- Saccharomyces cerevisiae Yca1 plays a critical role in protein quality control.
- Yca1 contributes to cellular fitness and adaptability through aggregate remodeling.
- This study reveals a novel non-apoptotic function for metacaspases in yeast.
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