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 H2O2to promote oxidative stress. We found that FeSOD2 is formed in cultured cells andin vivo. FeSOD2 causes mitochondrial dysfunction and higher levels of oxidative stress in cultured cells andin 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.

中文翻译：

---

缺锰细胞和小鼠中的线粒体超氧化物歧化酶转换为过氧化物过氧化物酶

在呼吸过程中会不断产生超氧自由基阴离子（O2⋅‒）和其他活性氧。在线粒体中，线粒体超氧化物歧化酶2（SOD2）加速了O2·‒的歧化，线粒体超氧化物歧化酶2（SOD2）是一种传统上与抗氧化保护相关的酶。但是，SOD2表达的增加会促进氧化应激，表明SOD2可能具有促氧化剂作用。在这里，我们显示了通常与锰结合的SOD2可以掺入铁并生成具有过氧化物酶活性的其他同种型。从锰到铁的转变使FeSOD2可以利用H2O2促进氧化应激。我们发现FeSOD2在培养的细胞和体内形成。FeSOD2在培养的细胞和体内导致线粒体功能障碍和较高水平的氧化应激。