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In Vivo Characterization of I91T Sod2 Polymorphism of Saccharomyces cerevisiae
Author(s) -
de Carvalho Mariana Dias Castela,
De Mesquita Joelma Freire,
Eleutherio Elis Cristina Araujo
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25720
Subject(s) - sod2 , superoxide dismutase , biology , mutant , sod1 , oxidative stress , biochemistry , microbiology and biotechnology , gene
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 sod2Δ Sod2I91T. In respiratory metabolism, sod2Δ Sod2WT and sod2Δ Sod2I91T showed high viability; although, sod2Δ Sod2I91T showed high percentage of cells with mitochondrial function compromised. Moreover, the fitness analysis of mixed cultures showed that sod2Δ Sod2I91T 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.