In Vivo Characterization of I91T Sod2 Polymorphism of Saccharomyces cerevisiae

Abstract

The mitochondrial antioxidant enzyme Mn-Superoxide Dismutase (Sod2) is essential for mammalian survival. I82T mutation in human Sod2 has been linked to a wide variety of diseases, including Alzheimer's and Parkinson's diseases as well as some types of cancers. Yeast wild-type (WT) Sod2 and the mutant Sod2 I91T, which corresponds to the human mutant Sod2 I82T, were cloned in sod2Δ strain. Residue I82 is conserved among a variety of species, showing that it has a biological importance. To assess the functionality of Sod2 I91T under oxidative stress, yeast cells were shifted from glucose (fermentative metabolism) to glycerol growth medium (respiratory metabolism). Overexpression of both Sod2 WT and Sod2 I91T increased Sod activity, but in long-term, the mutation brought impairment to Sod function. Aconitase, a sensor of superoxide radical production in vivo, had its activity preserved by overexpressions of both Sod2, in lesser extent in sod2ΔSod2I91T. In respiratory metabolism, sod2ΔSod2WT and sod2ΔSod2I91T showed high viability; although, sod2ΔSod2I91T showed high percentage of cells with mitochondrial function compromised. Moreover, the fitness analysis of mixed cultures showed that sod2ΔSod2I91T was less robust than WT cells. Although overexpression of Sod2 containing I91T mutation allows higher cell viability, longevity of cells is hampered, showing that in long-term this mutation is not neutral. J. Cell. Biochem. 118: 1078-1086, 2017. © 2016 Wiley Periodicals, Inc.

Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1

“…The plates had been incubated at 28 °C for 72 h, and the colonies were counted. Viability was determined before and after growth (47–49). Malondialdehyde, a final product of lipid peroxidation, was measured by thiobarbituric acid reactive species (TBARS) method (50).…”

Association of arsenic-relatedAS3MTgene and antioxidantSOD2gene expression in industrial workers occupationally exposed to arsenic

“…Millions of people are subjected to As poisoning from contaminated water and food resources (Li et al, 2015). Arsenicals exert toxicity by inactivating up to 200 enzymes, among which superoxide dismutase (SOD) is considered as the first line of mitochondrial defense against oxidative damage (De Carvalho et al, 2017). As toxicity is positively associated with DNA damage.…”

In silico analysis and molecular dynamics simulation of human superoxide dismutase 3 (SOD3) genetic variants

“…Despite the central role of SOD3 in oxidative stress effects, the complete SOD3 structure remains unresolved. 15 In this study, structural modeling, molecular dynamics (MD) simulations, and SNP functional predictions were applied, following the methodology previously established by our group 9,11,12 for an in silico analysis of the SOD3 protein and its natural variants. We aimed to conduct a thorough analysis of the protein structures, as well as the possible effects of structural changes in disease development.…”

“…This is believed to impair the subcellular localization of SOD2 . The A16V polymorphism has been associated with the development of Alzheimer's and Parkinson's diseases . Studies have shown that the I82T mutation decreases the SOD2 activity .…”