Cardiolipin deficiency in Barth syndrome is not associated with increased superoxide/H O production in heart and skeletal muscle mitochondria.

Barth syndrome (BTHS) is a rare X-linked genetic disorder caused by mutations in the gene encoding the transacylase tafazzin and characterized by loss of cardiolipin and severe cardiomyopathy. Mitochondrial oxidants have been implicated in the cardiomyopathy in BTHS. Eleven mitochondrial sites produce superoxide/hydrogen peroxide (H O ) at significant rates. Which of these sites generate oxidants at excessive rates in BTHS is unknown. Here, we measured the maximum capacity of superoxide/H O production from each site and the ex vivo rate of superoxide/H O production in the heart and skeletal muscle mitochondria of the tafazzin knockdown mice (tazkd) from 3 to 12 months of age. Despite reduced oxidative capacity, superoxide/H O production was indistinguishable between tazkd mice and wild-type littermates. These observations raise questions about the involvement of mitochondrial oxidants in BTHS pathology.