Utilization of Yeast To Investigate the Role of Lipid Oxidation in Cell Death

Abstract

The yeast Saccharomyces cerevisiae is a powerful tool to investigate several aspects of the molecular mechanisms underlying programmed cell death, namely, the events involving mitochondria. Yeast has allowed new information to be gained about crucial aspects of the interaction between proapoptotic proteins Bax and Bid and mitochondria, namely, their addressing and insertion into the mitochondrial outer membrane and their ability to induce the relocalization of cytochrome c. Going one step further, the prooxidant effect of Bax can also be studied in yeast. Bax expression induces both the accumulation of reactive oxygen species and lipid oxidation. Lipid oxidation is involved in Bax-induced cell death and may be required for optimal insertion of Bax in mitochondria. The easy modulation of lipid composition in yeast is a powerful tool to investigate this process further, and studies can be extended to other regulators of apoptosis, such as proapoptotic Bid or antiapoptotic Bcl-x_L. Also, yeast is a model for the study of other types of cell death, such as autophagy-related forms of death, for which a role of lipid oxidation has also been evidenced.