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

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1863; no. 8; pp. 857 - 865
• Main Authors: Lou, Wenjia, Reynolds, Christian A., Li, Yiran, Liu, Jenney, Hüttemann, Maik, Schlame, Michael, Stevenson, David, Strathdee, Douglas, Greenberg, Miriam L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2018
• Subjects: Animals; Barth syndrome; Barth Syndrome - genetics; Barth Syndrome - pathology; Cardiolipin; Cardiolipins - metabolism; Cell Differentiation - genetics; Cell Line; CRISPR-Cas Systems; Gene Knockout Techniques; Humans; Lysophospholipids - metabolism; Mice; Mitochondria - metabolism; Mitochondria - pathology; Models, Biological; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Myoblasts - cytology; Myoblasts - metabolism; Myoblasts - pathology; Myotube differentiation; Tafazzin; Transcription Factors - genetics; Transcription Factors - metabolism; Tafazzin; Barth syndrome; Myotube differentiation; Cardiolipin
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2018.04.015

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.
•A CRISPR-generated stable tafazzin knockout myoblast cell line has been constructed.•Tafazzin knockout cells exhibit mitochondrial deficits.•Tafazzin knockout cells are consistent with other models of Barth syndrome.•Tafazzin-deficiency was associated with impairment of myocyte differentiation.