Oxygen Stress: A Regulator of Apoptosis in Yeast

Oxygen Stress: A Regulator of Apoptosis in Yeast

Volume 145, Number 4, May 17, 1999 | Frank Madeo, Eleonore Fröhlich, Martin Ligr, Martin Grey, Stephan J. Sigrist, Dieter H. Wolf, and Kai-Uwe Fröhlich
The study investigates the role of oxygen radicals in apoptosis in *Saccharomyces cerevisiae*. Key findings include: 1. **Induction of Apoptosis**: Yeast cells can be induced to undergo apoptosis by depleting glutathione or exposing them to low concentrations of H₂O₂. The *cdc48* mutant and cells expressing mammalian *bax* also exhibit apoptotic markers, such as DNA fragmentation, chromatin condensation, and phosphatidylserine exposure. 2. **Role of Oxygen Radicals**: The accumulation of oxygen radicals (ROS) is crucial for the apoptotic process. ROS accumulation is prevented by radical scavengers or hypoxic conditions, suggesting that ROS are essential for apoptosis. 3. **Cycloheximide's Effect**: Cycloheximide, which inhibits protein synthesis, prevents the apoptotic effects of H₂O₂ and improves cell survival. This indicates that apoptosis involves active cellular participation. 4. **Glutathione Depletion**: A yeast strain lacking glutathione (GSH1 deletion) exhibits typical apoptotic markers, including DNA fragmentation and chromatin condensation, even in the absence of exogenous H₂O₂. 5. **Bax Expression**: Expression of *bax* in yeast results in ROS accumulation, which is prevented by coexpression of *bcl-XL*. This suggests that *bax* induces apoptosis through a mechanism involving ROS production. 6. **Anaerobic Conditions**: Anaerobic conditions or the use of radical scavengers can suppress the apoptotic effects of H₂O₂ and *bax* expression, indicating that ROS are critical for apoptosis. The study concludes that ROS play a central role in the apoptotic process in yeast, providing insights into the evolutionary origins of apoptosis and its regulation.The study investigates the role of oxygen radicals in apoptosis in *Saccharomyces cerevisiae*. Key findings include: 1. **Induction of Apoptosis**: Yeast cells can be induced to undergo apoptosis by depleting glutathione or exposing them to low concentrations of H₂O₂. The *cdc48* mutant and cells expressing mammalian *bax* also exhibit apoptotic markers, such as DNA fragmentation, chromatin condensation, and phosphatidylserine exposure. 2. **Role of Oxygen Radicals**: The accumulation of oxygen radicals (ROS) is crucial for the apoptotic process. ROS accumulation is prevented by radical scavengers or hypoxic conditions, suggesting that ROS are essential for apoptosis. 3. **Cycloheximide's Effect**: Cycloheximide, which inhibits protein synthesis, prevents the apoptotic effects of H₂O₂ and improves cell survival. This indicates that apoptosis involves active cellular participation. 4. **Glutathione Depletion**: A yeast strain lacking glutathione (GSH1 deletion) exhibits typical apoptotic markers, including DNA fragmentation and chromatin condensation, even in the absence of exogenous H₂O₂. 5. **Bax Expression**: Expression of *bax* in yeast results in ROS accumulation, which is prevented by coexpression of *bcl-XL*. This suggests that *bax* induces apoptosis through a mechanism involving ROS production. 6. **Anaerobic Conditions**: Anaerobic conditions or the use of radical scavengers can suppress the apoptotic effects of H₂O₂ and *bax* expression, indicating that ROS are critical for apoptosis. The study concludes that ROS play a central role in the apoptotic process in yeast, providing insights into the evolutionary origins of apoptosis and its regulation.
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