The peroxidase activity of mitochondrial superoxide dismutase

Free Radic Biol Med. 2013 Jan;54:116-24. doi: 10.1016/j.freeradbiomed.2012.08.573. Epub 2012 Aug 28.

Abstract

Manganese superoxide dismutase (MnSOD) is an integral mitochondrial protein known as a first-line antioxidant defense against superoxide radical anions produced as by-products of the electron transport chain. Recent studies have shaped the idea that by regulating the mitochondrial redox status and H(2)O(2) outflow, MnSOD acts as a fundamental regulator of cellular proliferation, metabolism, and apoptosis, thereby assuming roles that extend far beyond its proposed antioxidant functions. Accordingly, allelic variations of MnSOD that have been shown to augment levels of MnSOD in mitochondria result in a 10-fold increase in prostate cancer risk. In addition, epidemiologic studies indicate that reduced glutathione peroxidase activity along with increases in H(2)O(2) further increase cancer risk in the face of MnSOD overexpression. These facts led us to hypothesize that, like its Cu,ZnSOD counterpart, MnSOD may work as a peroxidase, utilizing H(2)O(2) to promote mitochondrial damage, a known cancer risk factor. Here we report that MnSOD indeed possesses peroxidase activity that manifests in mitochondria when the enzyme is overexpressed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydrogen Peroxide / metabolism
  • MCF-7 Cells
  • Mice
  • Microscopy, Electron
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Neoplasms / enzymology*
  • Oxidation-Reduction
  • Oxidative Stress
  • Peroxidase / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Risk
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxides / metabolism

Substances

  • Recombinant Proteins
  • Superoxides
  • Hydrogen Peroxide
  • Peroxidase
  • Superoxide Dismutase