RRC ID 46150
Author Leitch JM, Li CX, Baron JA, Matthews LM, Cao X, Hart PJ, Culotta VC.
Title Post-translational modification of Cu/Zn superoxide dismutase under anaerobic conditions.
Journal Biochemistry
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.
Volume 51(2)
Pages 677-85
Published 2012-1-17
DOI 10.1021/bi201353y
PMID 22148750
PMC PMC3264780
MeSH Anaerobiosis / drug effects Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans / growth & development Copper / metabolism* Enzyme Activation / drug effects Models, Molecular Molecular Chaperones / metabolism Oxygen / pharmacology Phosphorylation / drug effects Protein Conformation Protein Processing, Post-Translational* / drug effects Saccharomyces cerevisiae / drug effects Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae / growth & development Serine / metabolism Superoxide Dismutase / chemistry Superoxide Dismutase / metabolism* Superoxide Dismutase-1 Zinc / metabolism*
IF 2.952
Times Cited 7
C.elegans tm776