Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions

Jeffry M. Leitch, Cissy X. Li, J. Allen Baron, Lauren M. Matthews, Xiaohang Cao, P. John Hart, Valeria C. Culotta

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In eukaryotic organisms, the largely cytosolic copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) enzyme represents a key defense against reactive oxygen toxicity. Although much is known about the biology of this enzyme under aerobic conditions, less is understood regarding the effects of low oxygen levels on Cu/Zn SOD enzymes from diverse organisms. We show here that like bakers' yeast (Saccharomyces cerevisiae), adaptation of the multicellular Caenorhabditis elegans to growth at low oxygen levels involves strong downregulation of its Cu/Zn SOD. Much of this regulation occurs at the post-translational level where CCS-independent activation of Cu/Zn SOD is inhibited. Hypoxia inactivates the endogenous Cu/Zn SOD of C. elegans Cu/Zn SOD as well as a P144 mutant of S. cerevisiae Cu/Zn SOD (herein denoted Sod1p) that is independent of CCS. In our studies of S. cerevisiae Sod1p, we noted a post-translational modification to the inactive enzyme during hypoxia. Analysis of this modification by mass spectrometry revealed phosphorylation at serine 38. Serine 38 represents a putative proline-directed kinase target site located on a solvent-exposed loop that is positioned at one end of the Sod1p β-barrel, a region immediately adjacent to residues previously shown to influence CCS-dependent activation. Although phosphorylation of serine 38 is minimal when the Sod1p is abundantly active (e.g., high oxygen level), up to 50% of Sod1p can be phosphorylated when CCS activation of the enzyme is blocked, e.g., by hypoxia or low-copper conditions. Serine 38 phosphorylation can be a marker for inactive pools of Sod1p.

Original languageEnglish (US)
Pages (from-to)677-685
Number of pages9
JournalBiochemistry
Volume51
Issue number2
DOIs
StatePublished - Jan 17 2012

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Post Translational Protein Processing
Serine
Saccharomyces cerevisiae
Yeast
Phosphorylation
Oxygen
Caenorhabditis elegans
Enzymes
Chemical activation
Copper
Enzyme Activation
Proline
Zinc
Mass Spectrometry
Phosphotransferases
Down-Regulation
Mass spectrometry
Toxicity
Superoxide Dismutase-1
Superoxide Dismutase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Leitch, J. M., Li, C. X., Baron, J. A., Matthews, L. M., Cao, X., Hart, P. J., & Culotta, V. C. (2012). Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions. Biochemistry, 51(2), 677-685. https://doi.org/10.1021/bi201353y

Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions. / Leitch, Jeffry M.; Li, Cissy X.; Baron, J. Allen; Matthews, Lauren M.; Cao, Xiaohang; Hart, P. John; Culotta, Valeria C.

In: Biochemistry, Vol. 51, No. 2, 17.01.2012, p. 677-685.

Research output: Contribution to journalArticle

Leitch, JM, Li, CX, Baron, JA, Matthews, LM, Cao, X, Hart, PJ & Culotta, VC 2012, 'Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions', Biochemistry, vol. 51, no. 2, pp. 677-685. https://doi.org/10.1021/bi201353y
Leitch, Jeffry M. ; Li, Cissy X. ; Baron, J. Allen ; Matthews, Lauren M. ; Cao, Xiaohang ; Hart, P. John ; Culotta, Valeria C. / Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions. In: Biochemistry. 2012 ; Vol. 51, No. 2. pp. 677-685.
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