Molecular Biology Of Yeast
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We study the links between mitochondria dynamics, reactive oxygen species formation, stress response, and the cell cycle. For this we use the baker’s yeast Saccharomyces cerevisiae as a model organism. We also use yeast to study the mechanism of the toxicity of polyglutamine-driven protein aggregation a cellular level. Our most recent research interest is to apply yeast to study the mechanism of action of mitochondria-targeted antioxidants.
Mitochondria are highly dynamic organelles—they change their shapes according to cellular needs. Normally mitochondria are thread-like structures, while after stresses they fragment and form vesicles. We study the mechanism of the fragmentation and its role in cellular stress response. We have already established the function of several proteins during stress-induced mitochondrial fragmentation. One of these proteins, Ysp2, was found to mediate the formation of special mitochondrial structures where several electrically separated compartments are covered by a single outer membrane. Such structures appeared to affect the overall yeast cell stress resistance.
The mechanism of cell cycle orchestration is well studied for S. cerevisiae. However, now it is becoming clear that one cycle could not be same as the others, i.e. the first cell cycle of newly emerging budding could differ from subsequent cycles in many parameters. We have shown that the daughter cells during their first cell cycle are extremely vulnerable to stresses such as heat shock or acidic stress. It appeared that one function of Sir2p is to compensate this vulnerability at the cost of the stress resistance of the mother cells.
In recent years the role of intracellular reactive oxygen species (ROS) has been significantly reconsidered. It has become obvious that while being highly toxic, ROS also play beneficial roles in cells. Our recent results show that upregulated ROS could protect from genotoxic stress induced by a DNA-damaging agent. Second, it appeared that intracellular localization of ROS is highly important. To study this topic we use mitochondria-targeted antioxidants and their derivatives designed and synthesized in our institute. The mechanisms of formation and detoxification of intracellular ROS and the role of ROS in cell physiology are of our special interest.
Finally, we are interested in one issue which is partly philosophical. On one hand, it was shown that yeast can undergo programmed cell death. On the other hand, there is accumulating evidence that in higher organisms certain types of death including the one induced by senescence might be programmed. As for a unicellular organism programmed cell death means programmed suicide, there is chance for parallels between programmed death of yeast cells and programmed death(s) of multicellular organisms. Our scientific ambition (or should we say “fantasy”?) is to reveal the molecular mechanisms of such ancestral programs.