Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of ATP. ► The release of AIF and Endo G contributes importantly to cell death. ► Alterations of SOD1 or SOD2 levels alter menadione-induced neuronal cytotoxicity.