Extra-mitochondrial Cu/Zn superoxide dismutase (Sod1) is dispensable for protection against oxidative stress but mediates peroxide signaling in Saccharomyces cerevisiae

Abstract

Cu/Zn Superoxide Dismutase (Sod1) is a highly conserved and abundant metalloenzyme that catalyzes the disproportionation of superoxide radicals into hydrogen peroxide and molecular oxygen. As a consequence, Sod1 serves dual roles in oxidative stress protection and redox signaling by both scavenging cytotoxic superoxide radicals and producing hydrogen peroxide that can be used to oxidize and regulate the activity of downstream targets. However, the relative contributions of Sod1 to protection against oxidative stress and redox signaling are poorly understood. Using the model unicellular eukaryote, Baker's yeast, we found that only a small fraction of the total Sod1 pool is required for protection against superoxide toxicity and that this pool is localized to the mitochondrial intermembrane space. On the contrary, we find that much larger amounts of extra-mitochondrial Sod1 are critical for peroxide-mediated redox signaling. Altogether, our results force the re-evaluation of the physiological role of bulk Sod1 in redox biology; namely, we propose that the vast majority of Sod1 in yeast is utilized for peroxide-mediated signaling rather than superoxide scavenging.

Actin Cytoskeleton Regulation by the Yeast NADPH Oxidase Yno1p Impacts Processes Controlled by MAPK Pathways

“…A ∆yno1 ∆sod1 double mutant shows an increased wiskostatin sensitivity compared to the respective single gene deletions. Recently, it was demonstrated that vacuoles in a ∆sod1 background show elevated vacuolar fragmentation [ 97 ]. Experiments in the plant Arabidopsis thaliana demonstrate that the importance of ROS as second messengers in response to hyperosmotic shock are evolutionary conserved [ 98 ].…”

Copper/Zinc Superoxide Dismutase in Human Skin: Current Knowledge

“…In response to oxidative stress, high levels of H 2 O 2 promote Cu/Zn SOD nuclear translocation and as a transcription factor the enzyme regulates the expression of oxidative resistance and repair genes (44). In addition, in yeasts, only a small amount of Cu/Zn SOD was shown to scavenge superoxides while the majority of Cu/Zn SOD mediated peroxide signaling (45). There are as yet few similar investigations on vertebrate cells including human; it would therefore be of great interest to confirm the data obtained in Saccharomyces cerevisiae.…”

Expanded role of the Cu‐sensing transcription factor Mac1p in Candida albicans

“…Eukaryotes typically contain a Cu/Zn‐SOD1 in the cytosol and mitochondrial intermembrane space, and a distinct Mn‐SOD2 in the mitochondrial matrix. Mitochondrial SOD1 and SOD2 ensure protection against respiratory chain superoxide, while cytosolic Cu/Zn‐SOD1 can participate in cell signaling involving ROS (Weisiger and Fridovich, 1973; Jaarsma et al ., 2001; Okado‐Matsumoto and Fridovich, 2001; Sturtz et al ., 2001; Juarez et al ., 2008; Reddi and Culotta, 2013; Broxton and Culotta, 2016; Montllor‐Albalate et al ., 2019). Apparently unique to C. albicans and closely related fungi is a second Mn‐containing Sod3p in the cytosol (Lamarre et al ., 2001).…”