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The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation

The ATP demand required for muscle development is accommodated by elevations in mitochondrial biogenesis, through the co-ordinated activities of the nuclear and mitochondrial genomes. The most important transcriptional activator of the mitochondrial genome is mitochondrial transcription factor A (Tf...

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Autores principales: Collu-Marchese, Melania, Shuen, Michael, Pauly, Marion, Saleem, Ayesha, Hood, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613705/
https://www.ncbi.nlm.nih.gov/pubmed/26182383
http://dx.doi.org/10.1042/BSR20150073
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author Collu-Marchese, Melania
Shuen, Michael
Pauly, Marion
Saleem, Ayesha
Hood, David A.
author_facet Collu-Marchese, Melania
Shuen, Michael
Pauly, Marion
Saleem, Ayesha
Hood, David A.
author_sort Collu-Marchese, Melania
collection PubMed
description The ATP demand required for muscle development is accommodated by elevations in mitochondrial biogenesis, through the co-ordinated activities of the nuclear and mitochondrial genomes. The most important transcriptional activator of the mitochondrial genome is mitochondrial transcription factor A (Tfam); however, the regulation of Tfam expression during muscle differentiation is not known. Thus, we measured Tfam mRNA levels, mRNA stability, protein expression and localization and Tfam transcription during the progression of muscle differentiation. Parallel 2-fold increases in Tfam protein and mRNA were observed, corresponding with 2–3-fold increases in mitochondrial content. Transcriptional activity of a 2051 bp promoter increased during this differentiation period and this was accompanied by a 3-fold greater Tfam mRNA stabilization. Interestingly, truncations of the promoter at 1706 bp, 978 bp and 393 bp promoter all exhibited 2–3-fold higher transcriptional activity than the 2051 bp construct, indicating the presence of negative regulatory elements within the distal 350 bp of the promoter. Activation of AMP kinase augmented Tfam transcription within the proximal promoter, suggesting the presence of binding sites for transcription factors that are responsive to cellular energy state. During differentiation, the accumulating Tfam protein was progressively distributed to the mitochondrial matrix where it augmented the expression of mtDNA and COX (cytochrome c oxidase) subunit I, an mtDNA gene product. Our data suggest that, during muscle differentiation, Tfam protein levels are regulated by the availability of Tfam mRNA, which is controlled by both transcription and mRNA stability. Changes in energy state and Tfam localization also affect Tfam expression and action in differentiating myotubes.
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spelling pubmed-46137052016-09-13 The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation Collu-Marchese, Melania Shuen, Michael Pauly, Marion Saleem, Ayesha Hood, David A. Biosci Rep Original Papers The ATP demand required for muscle development is accommodated by elevations in mitochondrial biogenesis, through the co-ordinated activities of the nuclear and mitochondrial genomes. The most important transcriptional activator of the mitochondrial genome is mitochondrial transcription factor A (Tfam); however, the regulation of Tfam expression during muscle differentiation is not known. Thus, we measured Tfam mRNA levels, mRNA stability, protein expression and localization and Tfam transcription during the progression of muscle differentiation. Parallel 2-fold increases in Tfam protein and mRNA were observed, corresponding with 2–3-fold increases in mitochondrial content. Transcriptional activity of a 2051 bp promoter increased during this differentiation period and this was accompanied by a 3-fold greater Tfam mRNA stabilization. Interestingly, truncations of the promoter at 1706 bp, 978 bp and 393 bp promoter all exhibited 2–3-fold higher transcriptional activity than the 2051 bp construct, indicating the presence of negative regulatory elements within the distal 350 bp of the promoter. Activation of AMP kinase augmented Tfam transcription within the proximal promoter, suggesting the presence of binding sites for transcription factors that are responsive to cellular energy state. During differentiation, the accumulating Tfam protein was progressively distributed to the mitochondrial matrix where it augmented the expression of mtDNA and COX (cytochrome c oxidase) subunit I, an mtDNA gene product. Our data suggest that, during muscle differentiation, Tfam protein levels are regulated by the availability of Tfam mRNA, which is controlled by both transcription and mRNA stability. Changes in energy state and Tfam localization also affect Tfam expression and action in differentiating myotubes. Portland Press Ltd. 2015-06-25 /pmc/articles/PMC4613705/ /pubmed/26182383 http://dx.doi.org/10.1042/BSR20150073 Text en © 2015 Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article published by Portland Press Limited and distributed under the Creative Commons Attribution Licence 3.0. (http://creativecommons.org/licenses/by/3.0/)
spellingShingle Original Papers
Collu-Marchese, Melania
Shuen, Michael
Pauly, Marion
Saleem, Ayesha
Hood, David A.
The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title_full The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title_fullStr The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title_full_unstemmed The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title_short The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation
title_sort regulation of mitochondrial transcription factor a (tfam) expression during skeletal muscle cell differentiation
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613705/
https://www.ncbi.nlm.nih.gov/pubmed/26182383
http://dx.doi.org/10.1042/BSR20150073
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