Oxidative stress and programmed cell death in yeast

Abstract

Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed.

Keywords: aging; apoptosis; autophagy; mitophagy; necrosis; oxidative stress; yeast.

Figure 1

Cellular responses to oxidative stress in Saccharomyces cerevisiae. Oxidative stress, induced by the accumulation of reactive oxygen species (ROS) such as ${\text{O}}_2^{\bullet -},$ H₂O₂, and $\text{O}{\text{H}}^{\bullet }$, can elicit a range of stress responses in budding yeast cells, that either result in cell survival (shown in green) or cell death (shown in red). Stress signals relayed by ROS themselves (such as H₂O₂) can activate transcription factors which upregulate the expression of genes encoding enzymatic (such as catalases) and non-enzymatic antioxidants (such as GSH). These response mechanisms, together with the targeted removal of small, oxidized proteins by the ubiquitin-dependent proteasome system (UPS), help ensure the survival of cells. Additionally, cells can activate cytoprotective autophagic pathways (bordered in yellow) that remove irreparably oxidized macromolecules or dysfunctional organelles, such as mitochondria. However, an abnormally high degree of autophagy might also mediate programmed cell death (PCD). Finally, exposure of cells to severe oxidative insults can elicit lethal response pathways such as apoptosis, necrosis, and possibly other forms of PCD which have yet to be discovered.