The study reports the development of a novel antioxidant, mitoQ, which selectively targets mitochondria to block oxidative damage. MitoQ is a ubiquinone derivative covalently attached to a lipophilic triphenylphosphonium cation, allowing it to accumulate within mitochondria due to the large mitochondrial membrane potential. The ubiquinol moiety formed in mitochondria acts as an antioxidant, preventing lipid peroxidation and protecting mitochondria from oxidative stress. After detoxifying reactive oxygen species, the ubiquinol moiety is regenerated by the respiratory chain, enabling its antioxidant activity to be recycled. In cell culture studies, mitoQ protected mammalian cells from hydrogen peroxide-induced apoptosis but not from apoptosis induced by staurosporine or tumor necrosis factor-α. This suggests that mitochondrial oxidative stress may be a critical step in hydrogen peroxide-induced apoptosis but not for apoptosis induced by other stimuli. The findings demonstrate the feasibility of using mitochondrially targeted antioxidants to investigate the role of mitochondrial oxidative damage in apoptotic cell death.The study reports the development of a novel antioxidant, mitoQ, which selectively targets mitochondria to block oxidative damage. MitoQ is a ubiquinone derivative covalently attached to a lipophilic triphenylphosphonium cation, allowing it to accumulate within mitochondria due to the large mitochondrial membrane potential. The ubiquinol moiety formed in mitochondria acts as an antioxidant, preventing lipid peroxidation and protecting mitochondria from oxidative stress. After detoxifying reactive oxygen species, the ubiquinol moiety is regenerated by the respiratory chain, enabling its antioxidant activity to be recycled. In cell culture studies, mitoQ protected mammalian cells from hydrogen peroxide-induced apoptosis but not from apoptosis induced by staurosporine or tumor necrosis factor-α. This suggests that mitochondrial oxidative stress may be a critical step in hydrogen peroxide-induced apoptosis but not for apoptosis induced by other stimuli. The findings demonstrate the feasibility of using mitochondrially targeted antioxidants to investigate the role of mitochondrial oxidative damage in apoptotic cell death.