Loss of Tafazzin Results in Decreased Myoblast Differentiation in C2C12 Cells: A Myoblast Model of Barth Syndrome and Cardiolipin Deficiency

Overview

Journal Biochim Biophys Acta Mol Cell Biol Lipids

Publisher Elsevier

Specialties Biochemistry
Biophysics
Cell Biology

Date 2018 Apr 26

PMID 29694924

Citations 23

Authors

Wenjia Lou

Christian A Reynolds

Yiran Li

Jenney Liu

Maik Huttemann

Michael Schlame

David Stevenson

Douglas Strathdee

Miriam L Greenberg

Affiliations

Soon will be listed here.

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.

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