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Gene Review

SOD1  -  superoxide dismutase SOD1

Saccharomyces cerevisiae S288c

Synonyms: J1968, YJR104C
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Disease relevance of SOD1

  • This role of SOD1 in copper buffering appears unrelated to its superoxide scavenging activity, since the enzyme protected against copper toxicity in anaerobic as well as aerobic conditions [1].
  • Saccharomyces cerevisiae strains lacking copper-zinc superoxide dismutase, which is encoded by the SOD1 gene, are sensitive to oxidative stress and exhibit a variety of growth defects including hypersensitivity to dioxygen and to superoxide-generating drugs such as paraquat [2].
  • To restore the SOD catalytic activity but not the zinc-binding capability of the SOD1 polypeptide, we overexpressed Mn-SOD from Bacillus stearothermophilus in the cytoplasm of sod1Delta yeast [3].
  • These studies reveal that the level of mitochondrial and cytosolic protein carbonylation, the level of 8-OH-dG in mitochondrial and nuclear DNA, and the expression of SOD1 all increase transiently during a shift to anoxia [4].
  • Sequences encoding three copper-zinc superoxide dismutase (CuZnSOD) mutant proteins analogous to those coded for in familial amyotrophic lateral sclerosis (fALS) were constructed in the Saccharomyces cerevisiae CuZnSOD gene and expressed in yeast lacking CuZnSOD (sod1-) [5].

High impact information on SOD1

  • Gly85-->Arg CuZnSOD failed to rescue the oxygen-sensitive phenotype of sod1- yeast, but Gly93-->Ala CuZnSOD and Lys100-->Gly CuZnSOD were apparently fully functional in vivo [5].
  • We demonstrate here that expression of the yeast or monkey metallothionein proteins in the presence of copper suppresses the lactate growth defect and some other phenotypes associated with SOD1-deletion strains, indicating that copper metallothioneins substitute for copper-zinc superoxide dismutase in vivo to protect cells from oxygen toxicity [2].
  • We have found that in addition to these known phenotypes, SOD1-deletion strains fail to grow on agar containing the respiratory carbon source lactate [2].
  • We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1, or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to replication arrest and DNA damage in Saccharomyces cerevisiae [6].
  • Mutants of Saccharomyces cerevisiae lacking a functional SOD1 gene encoding Cu/Zn superoxide dismutase (SOD) are sensitive to atmospheric levels of oxygen and are auxotrophic for lysine and methionine when grown in air [7].

Chemical compound and disease context of SOD1

  • In addition to being hypersensitive to oxygen toxicity, strains containing deletions in both the SOD1 (encoding Cu/Zn-SOD) and SOD2 (encoding Mn-SOD) genes are defective in sporulation, are associated with a high mutation rate, and are unable to biosynthesize lysine and methionine [8].

Biological context of SOD1

  • Strains were transformed with yeast episomal plasmids (YEp) containing both PGK1 and SOD1 genes and were grown on fermentable carbon sources and under vigorous aeration [9].
  • Furthermore, utilizing reporter gene fusion constructs, we monitored the expression of the gamma-glutamylcysteinyl synthetase (encoded by GSH1) and the two superoxide dismutases (encoded by SOD1 and SOD2) during the metabolic transition from fermentation to respiration; and we detected an up-regulation of all three genes during the diauxic shift [10].
  • Insofar as ROS are very reactive and inherently unstable, a more reliable method for measuring changes in their intracellular levels is to measure their damage (e.g. the accumulation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in DNA, and oxidative protein carbonylation) or to measure the expression of an oxidative stress-induced gene, e.g. SOD1 [4].
  • The LYS7 gene in Saccharomyces cerevisiae encodes a protein (yCCS) that delivers copper to the active site of copper-zinc superoxide dismutase (CuZn-SOD, a product of the SOD1 gene) [3].
  • Induction by paraquat was modest, about 50% for SOD1 and 100% for SOD2; it was apparently independent of the respiratory chain function [11].

Anatomical context of SOD1

  • Saccharomyces cerevisiae expresses two forms of superoxide dismutase (SOD): MnSOD, encoded by SOD2, which is located within the mitochondrial matrix, and CuZnSOD, encoded by SOD1, which is located in both the cytosol and the mitochondrial intermembrane space [12].
  • O(2)(-) is known to oxidize and thus destabilize the [Fe-4S] clusters of dehydratases; hence, this would make perfect sense were it not for the fact that SOD1 localizes to the cytosol and the intermembrane space of mitochondria, whereas Lys4p localizes to the mitochondrial matrix [13].
  • Previously, we reported that the attenuation of sod1 mutant in mice was resulting from enhanced susceptibility to phagocyte killing, combined with a reduction in the activities of a number of virulence factors [14].

Associations of SOD1 with chemical compounds

  • Eukaryotes express both copper/zinc (SOD1)- and manganese (SOD2)-requiring superoxide dismutase enzymes that guard against oxidative damage [15].
  • We now demonstrate that CRS4 is equivalent to SOD1, encoding copper/zinc superoxide dismutase (SOD) [1].
  • This work reports the role of both superoxide dismutases-CuZnSOD (encoded by SOD1) and MnSOD (encoded by SOD2)-in the build-up of tolerance to ethanol during growth of Saccharomyces cerevisiae from exponential to post-diauxic phase [16].
  • Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors [6].
  • The protective effect of trehalose against oxidative damage produced by menadione was especially efficient under SOD1 deficiency [17].

Regulatory relationships of SOD1

  • Thus, we conclude that when Sod1p is absent a lysine auxotrophy is induced because Lys4p is inactivated in the matrix by superoxide that originates in the intermembrane space and diffuses across the inner membrane [18].

Other interactions of SOD1

  • Surprisingly, Lys4p does not share a compartment with Sod1p but is located in the mitochondrial matrix [18].
  • The activity of a second matrix protein, the tricarboxylic acid cycle enzyme aconitase, was similarly lowered in sod1 Delta mutants [18].
  • Located in the cytosol and intermembrane space of the mitochondria, Sod1p likely provides direct protection of the cytosolic enzyme Leu1p [18].
  • Matrix-targeted Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner membrane tethered human Sod1 [19].
  • The gene for SOD-1 (SOD1) was physically mapped by Southern blot to restriction fragments containing CDC11. scd1 failed to complement a complete deletion of SOD1 [20].

Analytical, diagnostic and therapeutic context of SOD1


  1. A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. Culotta, V.C., Joh, H.D., Lin, S.J., Slekar, K.H., Strain, J. J. Biol. Chem. (1995) [Pubmed]
  2. Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Tamai, K.T., Gralla, E.B., Ellerby, L.M., Valentine, J.S., Thiele, D.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. Evidence for a novel role of copper-zinc superoxide dismutase in zinc metabolism. Wei, J.P., Srinivasan, C., Han, H., Valentine, J.S., Gralla, E.B. J. Biol. Chem. (2001) [Pubmed]
  4. Exposure of yeast cells to anoxia induces transient oxidative stress. Implications for the induction of hypoxic genes. Dirmeier, R., O'Brien, K.M., Engle, M., Dodd, A., Spears, E., Poyton, R.O. J. Biol. Chem. (2002) [Pubmed]
  5. Characterization of three yeast copper-zinc superoxide dismutase mutants analogous to those coded for in familial amyotrophic lateral sclerosis. Nishida, C.R., Gralla, E.B., Valentine, J.S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. Carter, C.D., Kitchen, L.E., Au, W.C., Babic, C.M., Basrai, M.A. Mol. Cell. Biol. (2005) [Pubmed]
  7. Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase. Lapinskas, P.J., Cunningham, K.W., Liu, X.F., Fink, G.R., Culotta, V.C. Mol. Cell. Biol. (1995) [Pubmed]
  8. Yeast lacking superoxide dismutase. Isolation of genetic suppressors. Liu, X.F., Elashvili, I., Gralla, E.B., Valentine, J.S., Lapinskas, P., Culotta, V.C. J. Biol. Chem. (1992) [Pubmed]
  9. Studies on plasmid stability, cell metabolism and superoxide dismutase production by Pgk- strains of Saccharomyces cerevisiae. Ayub, M.A., Astolfi-Filho, S., Mavituna, F., Oliver, S.G. Appl. Microbiol. Biotechnol. (1992) [Pubmed]
  10. Diauxic shift-induced stress resistance against hydroperoxides in Saccharomyces cerevisiae is not an adaptive stress response and does not depend on functional mitochondria. Maris, A.F., Assumpção, A.L., Bonatto, D., Brendel, M., Henriques, J.A. Curr. Genet. (2001) [Pubmed]
  11. Regulation of Cu,Zn- and Mn-superoxide dismutase transcription in Saccharomyces cerevisiae. Galiazzo, F., Labbe-Bois, R. FEBS Lett. (1993) [Pubmed]
  12. Mitochondrial protein oxidation in yeast mutants lacking manganese-(MnSOD) or copper- and zinc-containing superoxide dismutase (CuZnSOD): evidence that MnSOD and CuZnSOD have both unique and overlapping functions in protecting mitochondrial proteins from oxidative damage. O'Brien, K.M., Dirmeier, R., Engle, M., Poyton, R.O. J. Biol. Chem. (2004) [Pubmed]
  13. Cross-compartment protection by SOD1. Liochev, S.I., Fridovich, I. Free Radic. Biol. Med. (2005) [Pubmed]
  14. Characterization of Cryptococcus neoformans variety gattii SOD2 reveals distinct roles of the two superoxide dismutases in fungal biology and virulence. Narasipura, S.D., Chaturvedi, V., Chaturvedi, S. Mol. Microbiol. (2005) [Pubmed]
  15. Manganese superoxide dismutase in Saccharomyces cerevisiae acquires its metal co-factor through a pathway involving the Nramp metal transporter, Smf2p. Luk, E.E., Culotta, V.C. J. Biol. Chem. (2001) [Pubmed]
  16. Mitochondrial superoxide dismutase is essential for ethanol tolerance of Saccharomyces cerevisiae in the post-diauxic phase. Costa, V., Amorim, M.A., Reis, E., Quintanilha, A., Moradas-Ferreira, P. Microbiology (Reading, Engl.) (1997) [Pubmed]
  17. Trehalose protects Saccharomyces cerevisiae from lipid peroxidation during oxidative stress. Herdeiro, R.S., Pereira, M.D., Panek, A.D., Eleutherio, E.C. Biochim. Biophys. Acta (2006) [Pubmed]
  18. Superoxide inhibits 4Fe-4S cluster enzymes involved in amino acid biosynthesis. Cross-compartment protection by CuZn-superoxide dismutase. Wallace, M.A., Liou, L.L., Martins, J., Clement, M.H., Bailey, S., Longo, V.D., Valentine, J.S., Gralla, E.B. J. Biol. Chem. (2004) [Pubmed]
  19. Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase. Cobine, P.A., Pierrel, F., Bestwick, M.L., Winge, D.R. J. Biol. Chem. (2006) [Pubmed]
  20. Genetic and biochemical characterization of Cu,Zn superoxide dismutase mutants in Saccharomyces cerevisiae. Chang, E.C., Crawford, B.F., Hong, Z., Bilinski, T., Kosman, D.J. J. Biol. Chem. (1991) [Pubmed]
  21. Copper- and zinc-containing superoxide dismutase and its gene from Candida albicans. Hwang, C.S., Rhie, G., Kim, S.T., Kim, Y.R., Huh, W.K., Baek, Y.U., Kang, S.O. Biochim. Biophys. Acta (1999) [Pubmed]
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