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  Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome.

Dudek, J., Cheng, I. F., Balleininger, M., Vaz, V. M., Streckfuss-Böhmeke, K., Hübscher, D., et al. (2013). Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome. Stem Cell Research, 11(2), 806-819. doi:10.1016/j.scr.2013.05.005.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-557A-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-C751-9
Genre: Journal Article

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 Creators:
Dudek, J., Author
Cheng, I. F., Author
Balleininger, M., Author
Vaz, V. M., Author
Streckfuss-Böhmeke, K., Author
Hübscher, D., Author
Vukotic, M., Author
Wanders, R. J. A., Author
Rehling, P.1, Author              
Guan, K., Author
Affiliations:
1Max Planck Fellow Peter Rehling, ou_1298545              

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 Abstract: Barth syndrome (BTHS) patients carrying mutations in tafazzin (TAZ1), which is involved in the final maturation of cardiolipin, present with dilated cardiomyopathy, skeletal myopathy, growth retardation and neutropenia. To study how mitochondrial function is impaired in BTHS patients, we generated induced pluripotent stem cells (iPSCs) to develop a novel and relevant human model system for BTHS. BTHS-iPSCs generated from dermal fibroblasts of three patients with different mutations in TAZ1 expressed pluripotency markers, and were able to differentiate into cells derived from all three germ layers both in vitro and in vivo. We used these cells to study the impact of tafazzin deficiency on mitochondria( oxidative phosphorylation. We found an impaired remodeling of cardiolipin, a dramatic decrease in basal oxygen consumption rate and in the maximal respiratory capacity in BTHS-iPSCs. Simultaneous measurement of extra-cellular acidification rate allowed us a thorough assessment of the metabolic deficiency in BTHS patients. Blue native gel analyses revealed that decreased respiration coincided with dramatic structural changes in respiratory chain supercomplexes leading to a massive increase in generation of reactive oxygen species. Our data demonstrate that BTHS-iPSCs are capable of modeling BTHS by recapitulating the disease phenotype and thus are important tools for studying the disease mechanism. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.

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Language(s): eng - English
 Dates: 2013-05-282013-09
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.scr.2013.05.005
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Title: Stem Cell Research
Source Genre: Journal
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Pages: - Volume / Issue: 11 (2) Sequence Number: - Start / End Page: 806 - 819 Identifier: -