Diminished exercise capacity and mitochondrial bc1 complex deficiency in tafazzin-knockdown mice

作者：Powers Corey; Huang Yan; Strauss Arnold; Khuchua Zaza^*

来源：Frontiers in Physiology, 2013, 4: 74.

DOI：10.3389/fphys.2013.00074

• Barth syndrome
• tafazzin
• complex-III
• cardiolipins
• exercise intolerance
• mouse models

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.

• 出版日期2013