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Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae

Shao-Rong Chen1, David D Dunigan, Martin B Dickman

  • 1Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0722, USA.

Free Radical Biology & Medicine
|May 3, 2003
PubMed

Insights

Selected antiapoptotic genes from other species protected baker's yeast against oxidative stress. These findings demonstrate the evolutionary conservation of programmed cell death pathways and highlight the protective role of Bcl-2 family proteins.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Oxidative stress induces cell death with apoptotic characteristics in wild-type yeast (Saccharomyces cerevisiae).
  • The Bcl-2 protein family plays a crucial role in regulating programmed cell death in various organisms.

Purpose of the Study:

  • To investigate the cytoprotective effects of selected antiapoptotic genes against oxidative stress in yeast.
  • To explore the evolutionary conservation and functional similarity of apoptosis-related genes across eukaryotes.

Main Methods:

  • Expression of nematode ced-9, human bcl-2, and chicken bcl-xl genes in Saccharomyces cerevisiae.
  • Exposure of engineered yeast strains to reactive oxygen species (ROS)-generating agents (H(2)O(2), menadione) and heat shock.
  • Evaluation of cell viability and apoptotic-like characteristics in response to stress treatments.

Main Results:

  • Yeast strains expressing ced-9, bcl-2, or bcl-xl genes exhibited significant tolerance to oxidative stress and heat shock.
  • These transformants did not display apoptotic features and remained viable under lethal conditions for wild-type yeast.
  • A nonfunctional mutant bcl-2 gene (bcl-2 deltaalpha 5-6) failed to confer protection, confirming the specific role of functional antiapoptotic proteins.

Conclusions:

  • The nematode CED-9 protein provides cytoprotection against oxidative stress in yeast, extending the known functions of the Bcl-2 family.
  • Bcl-2 family members protect yeast from physiological stresses, supporting their conserved role in modulating programmed cell death.
  • These findings underscore the broad evolutionary conservation and functional similarity of apoptotic processes in eukaryotic organisms.

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