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Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery

Publication ,  Journal Article
Suzuki-Hatano, S; Sriramvenugopal, M; Ramanathan, M; Soustek, M; Byrne, BJ; Cade, WT; Kang, PB; Pacak, CA
Published in: International Journal of Molecular Sciences
July 11, 2019

Barth syndrome (BTHS) is a rare, X-linked, mitochondrial disorder caused by mutations in the gene encoding tafazzin. BTHS results in cardiomyopathy, muscle fatigue, and neutropenia in patients. Tafazzin is responsible for remodeling cardiolipin, a key structural lipid of the inner mitochondrial membrane. As symptoms can vary in severity amongst BTHS patients, we sought to compare mtDNA copy numbers, mitochondrial fragmentation, and functional parameters between primary dermal BTHS fibroblasts isolated from patients with two different mutations in the TAZ locus. To confirm cause‒effect relationships and further support the development of gene therapy for BTHS, we also characterized the BTHS cells following adeno-associated virus (AAV)-TAZ transduction. Our data show that, in response to AAV-TAZ transduction, these remarkably dynamic organelles show recovery of mtDNA copy numbers, mitochondrial structure, and mitochondrial function, providing additional evidence to support the therapeutic potential of AAV-mediated gene delivery for BTHS. This study also demonstrates the direct relationship between healthy mitochondrial membrane structure and maintenance of proper levels of mtDNA copy numbers.

Duke Scholars

Published In

International Journal of Molecular Sciences

DOI

EISSN

1422-0067

Publication Date

July 11, 2019

Volume

20

Issue

14

Start / End Page

3416 / 3416

Publisher

MDPI AG

Related Subject Headings

  • Chemical Physics
  • 0699 Other Biological Sciences
  • 0604 Genetics
  • 0399 Other Chemical Sciences
 

Citation

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Suzuki-Hatano, S., Sriramvenugopal, M., Ramanathan, M., Soustek, M., Byrne, B. J., Cade, W. T., … Pacak, C. A. (2019). Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery. International Journal of Molecular Sciences, 20(14), 3416–3416. https://doi.org/10.3390/ijms20143416
Suzuki-Hatano, Silveli, Mughil Sriramvenugopal, Manash Ramanathan, Meghan Soustek, Barry J. Byrne, W Todd Cade, Peter B. Kang, and Christina A. Pacak. “Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery.” International Journal of Molecular Sciences 20, no. 14 (July 11, 2019): 3416–3416. https://doi.org/10.3390/ijms20143416.
Suzuki-Hatano S, Sriramvenugopal M, Ramanathan M, Soustek M, Byrne BJ, Cade WT, et al. Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery. International Journal of Molecular Sciences. 2019 Jul 11;20(14):3416–3416.
Suzuki-Hatano, Silveli, et al. “Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery.” International Journal of Molecular Sciences, vol. 20, no. 14, MDPI AG, July 2019, pp. 3416–3416. Crossref, doi:10.3390/ijms20143416.
Suzuki-Hatano S, Sriramvenugopal M, Ramanathan M, Soustek M, Byrne BJ, Cade WT, Kang PB, Pacak CA. Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery. International Journal of Molecular Sciences. MDPI AG; 2019 Jul 11;20(14):3416–3416.

Published In

International Journal of Molecular Sciences

DOI

EISSN

1422-0067

Publication Date

July 11, 2019

Volume

20

Issue

14

Start / End Page

3416 / 3416

Publisher

MDPI AG

Related Subject Headings

  • Chemical Physics
  • 0699 Other Biological Sciences
  • 0604 Genetics
  • 0399 Other Chemical Sciences