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Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development
The mitochondrial phospholipid cardiolipin (CL) is critical for numerous essential biological processes, including mitochondrial dynamics and energy metabolism. Mutations in the CL remodeling enzyme TAFAZZIN cause Barth syndrome, a life-threatening genetic disorder that results in severe physiologic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999232/ https://www.ncbi.nlm.nih.gov/pubmed/36739949 http://dx.doi.org/10.1016/j.jbc.2023.102978 |
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author | Vo, Linh Schmidtke, Michael W. Da Rosa-Junior, Nevton T. Ren, Mindong Schlame, Michael Greenberg, Miriam L. |
author_facet | Vo, Linh Schmidtke, Michael W. Da Rosa-Junior, Nevton T. Ren, Mindong Schlame, Michael Greenberg, Miriam L. |
author_sort | Vo, Linh |
collection | PubMed |
description | The mitochondrial phospholipid cardiolipin (CL) is critical for numerous essential biological processes, including mitochondrial dynamics and energy metabolism. Mutations in the CL remodeling enzyme TAFAZZIN cause Barth syndrome, a life-threatening genetic disorder that results in severe physiological defects, including cardiomyopathy, skeletal myopathy, and neutropenia. To study the molecular mechanisms whereby CL deficiency leads to skeletal myopathy, we carried out transcriptomic analysis of the TAFAZZIN-knockout (TAZ-KO) mouse myoblast C2C12 cell line. Our data indicated that cardiac and muscle development pathways are highly decreased in TAZ-KO cells, consistent with a previous report of defective myogenesis in this cell line. Interestingly, the muscle transcription factor myoblast determination protein 1 (MyoD1) is significantly repressed in TAZ-KO cells and TAZ-KO mouse hearts. Exogenous expression of MyoD1 rescued the myogenesis defects previously observed in TAZ-KO cells. Our data suggest that MyoD1 repression is caused by upregulation of the MyoD1 negative regulator, homeobox protein Mohawk, and decreased Wnt signaling. Our findings reveal, for the first time, that CL metabolism regulates muscle differentiation through MyoD1 and identify the mechanism whereby MyoD1 is repressed in CL-deficient cells. |
format | Online Article Text |
id | pubmed-9999232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-99992322023-03-11 Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development Vo, Linh Schmidtke, Michael W. Da Rosa-Junior, Nevton T. Ren, Mindong Schlame, Michael Greenberg, Miriam L. J Biol Chem Research Article The mitochondrial phospholipid cardiolipin (CL) is critical for numerous essential biological processes, including mitochondrial dynamics and energy metabolism. Mutations in the CL remodeling enzyme TAFAZZIN cause Barth syndrome, a life-threatening genetic disorder that results in severe physiological defects, including cardiomyopathy, skeletal myopathy, and neutropenia. To study the molecular mechanisms whereby CL deficiency leads to skeletal myopathy, we carried out transcriptomic analysis of the TAFAZZIN-knockout (TAZ-KO) mouse myoblast C2C12 cell line. Our data indicated that cardiac and muscle development pathways are highly decreased in TAZ-KO cells, consistent with a previous report of defective myogenesis in this cell line. Interestingly, the muscle transcription factor myoblast determination protein 1 (MyoD1) is significantly repressed in TAZ-KO cells and TAZ-KO mouse hearts. Exogenous expression of MyoD1 rescued the myogenesis defects previously observed in TAZ-KO cells. Our data suggest that MyoD1 repression is caused by upregulation of the MyoD1 negative regulator, homeobox protein Mohawk, and decreased Wnt signaling. Our findings reveal, for the first time, that CL metabolism regulates muscle differentiation through MyoD1 and identify the mechanism whereby MyoD1 is repressed in CL-deficient cells. American Society for Biochemistry and Molecular Biology 2023-02-04 /pmc/articles/PMC9999232/ /pubmed/36739949 http://dx.doi.org/10.1016/j.jbc.2023.102978 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Vo, Linh Schmidtke, Michael W. Da Rosa-Junior, Nevton T. Ren, Mindong Schlame, Michael Greenberg, Miriam L. Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title | Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title_full | Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title_fullStr | Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title_full_unstemmed | Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title_short | Cardiolipin metabolism regulates expression of muscle transcription factor MyoD1 and muscle development |
title_sort | cardiolipin metabolism regulates expression of muscle transcription factor myod1 and muscle development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999232/ https://www.ncbi.nlm.nih.gov/pubmed/36739949 http://dx.doi.org/10.1016/j.jbc.2023.102978 |
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