Comparing the yeast retrograde response and NF-κB stress responses: implications for aging

The mitochondrial retrograde response has been extensively described in Saccharomyces cerevisiae, where it has been found to extend life span during times of mitochondrial dysfunction, damage or low nutrient levels. In yeast, the retrograde response genes (RTG) convey these stress responses to the nucleus to change the gene expression adaptively. Similarly, most classes of higher organisms have been shown to have some version of a central stress-mediating transcription factor, NF-κB. There have been several modifications along the phylogenetic tree as NF-κB has taken a larger role in managing cellular stresses. Here, we review similarities and differences in mechanisms and pathways between RTG genes in yeast and NF-κB as seen in more complex organisms. We perform a structural homology search and reveal similarities of Rtg proteins with eukaryotic transcription factors involved in development and metabolism. NF-κB shows more sophisticated functions when compared to RTG genes including participation in immune responses and induction of apoptosis under high levels of ROS-induced mitochondrial and nuclear DNA damage. Involvement of NF-κB in chromosomal stability, coregulation of mitochondrial respiration, and cross talk with the TOR (target of rapamycin) pathway points to a conserved mechanism also found in yeast.