title: Diminished Exercise Capacity and Mitochondrial bc1 Complex Deficiency in Tafazzin-Knockdown Mice.
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.
authors.affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center Cincinnati, OH, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Powers
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Arnold
authors.initials: A
authors.lastname: Strauss
authors.forename: Zaza
authors.initials: Z
authors.lastname: Khuchua
keywords: Barth syndrome; cardiolipins; complex-III; exercise intolerance; mouse models; tafazzin