Activation of superoxide dismutases: Putting the metal to the pedal

Valeria Cizewski Culotta*, Mei Yang, Thomas V. O'Halloran

*Corresponding author for this work

Research output: Contribution to journalReview article

338 Scopus citations

Abstract

Superoxide dismutases (SOD) are important anti-oxidant enzymes that guard against superoxide toxicity. Various SOD enzymes have been characterized that employ either a copper, manganese, iron or nickel co-factor to carry out the disproportionation of superoxide. This review focuses on the copper and manganese forms, with particular emphasis on how the metal is inserted in vivo into the active site of SOD. Copper and manganese SODs diverge greatly in sequence and also in the metal insertion process. The intracellular copper SODs of eukaryotes (SOD1) can obtain copper post-translationally, by way of interactions with the CCS copper chaperone. CCS also oxidizes an intrasubunit disulfide in SOD1. Adventitious oxidation of the disulfide can lead to gross misfolding of immature forms of SOD1, particularly with SOD1 mutants linked to amyotrophic lateral sclerosis. In the case of mitochondrial MnSOD of eukaryotes (SOD2), metal insertion cannot occur post-translationally, but requires new synthesis and mitochondrial import of the SOD2 polypeptide. SOD2 can also bind iron in vivo, but is inactive with iron. Such metal ion mis-incorporation with SOD2 can become prevalent upon disruption of mitochondrial metal homeostasis. Accurate and regulated metallation of copper and manganese SOD molecules is vital to cell survival in an oxygenated environment.

Original languageEnglish (US)
Pages (from-to)747-758
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1763
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • ALS
  • CCS
  • Copper
  • Copper chaperone
  • Disulfide isomerase
  • EC-SOD
  • Iron
  • Manganese
  • Mitochondria
  • Posttranslational modification
  • SOD
  • SOD1
  • SOD2
  • Superoxide dismutase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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