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.

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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