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Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency.

Authors
  • Lou, Wenjia1
  • Reynolds, Christian A1
  • Li, Yiran1
  • Liu, Jenney2
  • Hüttemann, Maik2
  • Schlame, Michael3
  • Stevenson, David4
  • Strathdee, Douglas4
  • Greenberg, Miriam L5
  • 1 Department of Biological Sciences, Wayne State University, Detroit, MI, USA.
  • 2 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
  • 3 Department of Anesthesiology and Cell Biology, New York University School of Medicine, New York, NY, USA.
  • 4 Transgenic Technology Laboratory, Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, United Kingdom. , (United Kingdom)
  • 5 Department of Biological Sciences, Wayne State University, Detroit, MI, USA. Electronic address: [email protected]
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Publisher
Elsevier
Publication Date
Aug 01, 2018
Volume
1863
Issue
8
Pages
857–865
Identifiers
DOI: 10.1016/j.bbalip.2018.04.015
PMID: 29694924
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Barth syndrome (BTHS) is an X-linked genetic disorder resulting from mutations in the tafazzin gene (TAZ), which encodes the transacylase that remodels the mitochondrial phospholipid cardiolipin (CL). While most BTHS patients exhibit pronounced skeletal myopathy, the mechanisms linking defective CL remodeling and skeletal myopathy have not been determined. In this study, we constructed a CRISPR-generated stable tafazzin knockout (TAZ-KO) C2C12 myoblast cell line. TAZ-KO cells exhibit mitochondrial deficits consistent with other models of BTHS, including accumulation of monolyso-CL (MLCL), decreased mitochondrial respiration, and increased mitochondrial ROS production. Additionally, tafazzin deficiency was associated with impairment of myocyte differentiation. Future studies should determine whether alterations in myogenic determination contribute to the skeletal myopathy observed in BTHS patients. The BTHS myoblast model will enable studies to elucidate mechanisms by which defective CL remodeling interferes with normal myocyte differentiation and skeletal muscle ontogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

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