Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8301288 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2018 | 28 Pages |
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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Authors
Wenjia Lou, Christian A. Reynolds, Yiran Li, Jenney Liu, Maik Hüttemann, Michael Schlame, David Stevenson, Douglas Strathdee, Miriam L. Greenberg,