RTG1- and RTG2-dependent retrograde signaling controls mitochondrial activity and stress resistance in Saccharomyces cerevisiae

• The mitochondrial properties of WT S. cerevisiae and mutants defective in RTG-dependent retrograde signaling were compared.
• Mitochondrial activity and mass are increased in mutants compared to WT.
• WT mitochondria release more H2O2 than those of the RTG mutants.
• WT cells are better able to decompose H2O2 and maintain viability when challenged with H2O2.
• RTG-dependent signaling is involved in the generation of an antioxidant response through hormesis.

Mitochondrial retrograde signaling is a communication pathway between the mitochondrion and the nucleus that regulates the expression of a subset of nuclear genes that codify mitochondrial proteins, mediating cell response to mitochondrial dysfunction. In Saccharomyces cerevisiae, the pathway depends on Rtg1p and Rtg3p, which together form the transcription factor that regulates gene expression, and Rtg2p, an activator of the pathway. Here, we provide novel studies aimed at assessing the functional impact of the lack of RTG-dependent signaling on mitochondrial activity. We show that mutants defective in RTG-dependent retrograde signaling present higher oxygen consumption and reduced hydrogen peroxide release in the stationary phase compared to wild-type cells. Interestingly, RTG mutants are less able to decompose hydrogen peroxide or maintain viability when challenged with hydrogen peroxide. Overall, our results indicate that RTG signaling is involved in the hormetic induction of antioxidant defenses and stress resistance.