Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice.

ABSTRACT: 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 mitochond

SUBMITTER: Ganini D 

PROVIDER: S-EPMC5910218 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature