A metacaspase of Trypanosoma brucei causes loss of respiration competence and clonal death in the yeast Saccharomyces cerevisiae

FEBS Lett. 2002 Apr 24;517(1-3):144-50. doi: 10.1016/s0014-5793(02)02608-x.

Abstract

Metacaspases constitute a new group of cysteine proteases homologous to caspases. Heterologous expression of Trypanosoma brucei metacaspase TbMCA4 in the budding yeast Saccharomyces cerevisiae resulted in growth inhibition, mitochondrial dysfunction and clonal death. The metacaspase orthologue of yeast, ScMCA1 (YOR197w), exhibited genetic interaction with WWM1 (YFL010c), which encodes a small WW domain protein. WWM1 overexpression resulted in growth arrest and clonal death, which was suppressed by concomitant overexpression of ScMCA1. GFP-fusion reporters of WWM1, ScMCA1 and TbMCA4 localized to the nucleus. Taken together, we suggest that metacaspases may play a role in nuclear function controlling cellular proliferation coupled to mitochondrial biogenesis.

MeSH terms

  • Animals
  • Caspases / genetics
  • Caspases / pharmacology*
  • Caspases / physiology*
  • Cell Death / physiology
  • Cell Division / drug effects
  • Cell Nucleus / enzymology
  • Cysteine Endopeptidases / classification
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / pharmacology
  • Gene Deletion
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Transfection
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Saccharomyces cerevisiae Proteins
  • Caspases
  • Cysteine Endopeptidases
  • MCA1 protein, S cerevisiae