by Fernanda M. Cunha
Mitochondria are believed to be former free living bacteria that established a successful symbiotic relationship with eukaryotic cells in such a way that today, besides being crucial for the biosynthesis of intermediary metabolites, calcium homeostasis, coordination of apoptosis and ATP synthesis, most mitochondrial proteins are encoded by nuclear rather than mitochondrial DNA. In that scenario, communication pathways that relay signals from the nucleus to mitochondria as well as from mitochondria to the nucleus (the retrograde way) are mandatory to secure energetic and metabolic homeostasis. In yeast, the best characterized retrograde signaling pathway, activated whenever there is some mitochondrial dysfunction, is the one dependent on RTG1, RTG2 and RTG3 proteins. Previous studies have shown that upon activation, RTG-dependent signaling leads to nuclear transcription of a number of genes with the purpose of adjusting cell metabolism to sustain survival even in the absence of a fully functioning Krebs cycle.
In a recently published article, Torelli et al. , describe interesting outcomes of retrograde signaling activation. The authors used yeast cells defective in RTG1 or 2 and showed that in the late stationary phase (when the cells are still alive but ceased multiplying due to glucose exhaustion in the culture medium) the mutants consumed twice of the oxygen/min when compared to wild type cells, suggesting an increased mitochondrial content. Additional assays demonstrated that mitochondria were indeed increased in mutants and the likely reason for this finding is that the mutants were less able to degrade mitochondria by mitophagy when compared to wild type cells. It is interesting to note that wild type cells’ mitochondria that escaped mitophagy produce significantly more hydrogen peroxide than those from RTG mutants. This is an intriguing finding, since mitophagy has been described as a strategy to eliminate dysfunctional and thus highly oxidant mitochondria. This increased hydrogen peroxide production by wild type cells’ mitochondria proved to be beneficial, as Torelli et al.  found out that wild type cells had increased catalase and glutathione peroxidase activities, making them more capable of degrading exogenous hydrogen peroxide and surviving after hydrogen peroxide challenge when compared to RTG mutant cells. Taken together, the results indicate that besides controlling mitochondrial activity, RTG-dependent retrograde signaling is determinant for the mounting of a redox resistance response through hormesis in stationary yeast cells.
- N. Q. Torelli, J. R. Ferreira-Júnior, A. J. Kowaltowski, F. M. da Cunha.
RTG1- and RTG2-dependent retrograde signaling controls mitochondrial activity and stress resistance in Saccharomyces cerevisiae.
Free Radical Biology & Medicine, 81: 30-7, 2015. | http://dx.doi.org/10.1016/j.freeradbiomed.2014.12.025
Fernanda Marques da Cunha, Ph.D.
Professor at Department of Biochemistry, Paulista School of Medicine,
Federal University of São Paulo, Brazil.