Tafazzin, a mitochondrial acyltransferase, plays an important role in 
cardiolipin side chain remodeling. Previous studies have shown that dysfunction 
of tafazzin reduces cardiolipin content, impairs mitochondrial function, and 
causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) 
have been implicated in the development of cardiomyopathy and are also the 
obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown 
increases ROS production from mitochondria, and a mitochondria-targeted 
antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac 
dysfunction. We employed cardiac myocytes transduced with an adenovirus 
containing tafazzin shRNA as a model to investigate the effects of the 
mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady 
state levels of cardiolipin and increased mitochondrial ROS. Treatment of 
cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced 
mitochondrial ROS production and cellular ATP decline. Mito-Tempo also 
significantly abrogated tafazzin knockdown induced cardiac hypertrophy, 
contractile dysfunction, and cell death. We conclude that mitochondria-targeted 
antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in 
cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth 
syndrome and other dilated cardiomyopathies resulting from mitochondrial 
oxidative stress.