Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. Cell Chem Biol 2018 Apr 19;25(4):413-425.e6
Date
02/06/2018Pubmed ID
29398562Pubmed Central ID
PMC5910218DOI
10.1016/j.chembiol.2018.01.007Scopus ID
2-s2.0-85045742134 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
Superoxide radical anion (O2⋅‒) and other reactive oxygen species are constantly produced during respiration. In mitochondria, the dismutation of O2⋅‒ is accelerated by the mitochondrial superoxide dismutase 2 (SOD2), an enzyme that has been traditionally associated with antioxidant protection. However, increases in SOD2 expression promote oxidative stress, indicating that there may be a prooxidant role for SOD2. Here we show that SOD2, which normally binds manganese, can incorporate iron and generate an alternative isoform with peroxidase activity. The switch from manganese to iron allows FeSOD2 to utilize H2O2 to promote oxidative stress. We found that FeSOD2 is formed in cultured cells and in vivo. FeSOD2 causes mitochondrial dysfunction and higher levels of oxidative stress in cultured cells and in vivo. We show that formation of FeSOD2 converts an antioxidant defense into a prooxidant peroxidase that leads to cellular changes seen in multiple human diseases.
Author List
Ganini D, Santos JH, Bonini MG, Mason RPMESH terms used to index this publication - Major topics in bold
AnimalsHumans
Hydrogen Peroxide
Iron
MCF-7 Cells
Manganese
Mice
Mice, Inbred C57BL
Mitochondria
Oxidative Stress
Peroxidase
Reactive Oxygen Species
Superoxide Dismutase
