{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T03:14:19Z","timestamp":1776395659501,"version":"3.51.2"},"reference-count":31,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T00:00:00Z","timestamp":1562803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002651","name":"Barth Syndrome Foundation","doi-asserted-by":"publisher","award":["AGR DTD 03-06-2015"],"award-info":[{"award-number":["AGR DTD 03-06-2015"]}],"id":[{"id":"10.13039\/100002651","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["#17SDG33410467"],"award-info":[{"award-number":["#17SDG33410467"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL107406-01A1"],"award-info":[{"award-number":["R01 HL107406-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL136759-01A1"],"award-info":[{"award-number":["R01 HL136759-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2012effect 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.<\/jats:p>","DOI":"10.3390\/ijms20143416","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T11:28:28Z","timestamp":1562844508000},"page":"3416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-TAZ Gene Delivery"],"prefix":"10.3390","volume":"20","author":[{"given":"Silveli","family":"Suzuki-Hatano","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mughil","family":"Sriramvenugopal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manash","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"Soustek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Todd","family":"Cade","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina A.","family":"Pacak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.bbamem.2009.07.009","article-title":"The enigmatic role of tafazzin in cardiolipin metabolism","volume":"1788","author":"Houtkooper","year":"2009","journal-title":"Biochim. 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