Next Article in Journal
Advances in the Uptake and Transport Mechanisms and QTLs Mapping of Cadmium in Rice
Previous Article in Journal
N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
Previous Article in Special Issue
Protective Effects of Euthyroidism Restoration on Mitochondria Function and Quality Control in Cardiac Pathophysiology
Article Menu

Export Article

Open AccessArticle

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

1
Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA
2
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
3
Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO 63110, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3416; https://doi.org/10.3390/ijms20143416
Received: 16 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 11 July 2019
(This article belongs to the Special Issue mtDNA and Mitochondrial Stress Signaling in Human Diseases)
  |  
PDF [18151 KB, uploaded 11 July 2019]
  |  

Abstract

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. View Full-Text
Keywords: Barth syndrome; mitochondrial disease; mtDNA copy numbers; gene therapy; AAV; TMEM65; fibroblasts Barth syndrome; mitochondrial disease; mtDNA copy numbers; gene therapy; AAV; TMEM65; fibroblasts
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Suzuki-Hatano, S.; Sriramvenugopal, M.; Ramanathan, M.; Soustek, M.; Byrne, B.J.; Cade, W.T.; Kang, P.B.; Pacak, C.A. Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery. Int. J. Mol. Sci. 2019, 20, 3416.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top