AUTHOR=Powers Corey , Huang Yan , Strauss Arnold W., Khuchua Zaza TITLE=Diminished Exercise Capacity and Mitochondrial bc1 Complex Deficiency in Tafazzin-Knockdown Mice JOURNAL=Frontiers in Physiology VOLUME=4 YEAR=2013 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2013.00074 DOI=10.3389/fphys.2013.00074 ISSN=1664-042X ABSTRACT=

The phospholipid, cardiolipin, is essential for maintaining mitochondrial structure and optimal function. Cardiolipin-deficiency in humans, Barth syndrome, is characterized by exercise intolerance, dilated cardiomyopathy, neutropenia, and 3-methyl-glutaconic aciduria. The causative gene is the mitochondrial acyl-transferase, tafazzin, that is essential for remodeling acyl chains of cardiolipin. We sought to determine metabolic rates in tafazzin-deficient mice during resting and exercise, and investigate the impact of cardiolipin-deficiency on mitochondrial respiratory chain activities. Tafazzin-knockdown in mice markedly impaired oxygen consumption rates during an exercise, without any significant effect on resting metabolic rates. CL-deficiency resulted in significant reduction of mitochondrial respiratory reserve capacity in neonatal cardiomyocytes that is likely to be caused by diminished activity of complex-III, which requires CL for its assembly and optimal activity. Our results may provide mechanistic insights of Barth syndrome pathogenesis.