The peroxidase activity of mitochondrial superoxide dismutase. Free Radic Biol Med 2013 Jan;54:116-24
Date
09/18/2012Pubmed ID
22982047Pubmed Central ID
PMC4155036DOI
10.1016/j.freeradbiomed.2012.08.573Scopus ID
2-s2.0-84871922397 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
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.
Author List
Ansenberger-Fricano K, Ganini D, Mao M, Chatterjee S, Dallas S, Mason RP, Stadler K, Santos JH, Bonini MGMESH terms used to index this publication - Major topics in bold
AnimalsGene Expression Regulation, Neoplastic
Humans
Hydrogen Peroxide
MCF-7 Cells
Mice
Microscopy, Electron
Mitochondria
Neoplasms
Oxidation-Reduction
Oxidative Stress
Peroxidase
Recombinant Proteins
Risk
Superoxide Dismutase
Superoxides
