CREB-1α is recruited to and mediates upregulation of the cytochrome c promoter during enhanced mitochondrial biogenesis accompanying skeletal muscle differentiation

Andras Franko, Sabine Mayer, Gerald Thiel, Ludovic Mercy, Thierry Arnould, Hue Tran Hornig-Do, Rudolf J. Wiesner, Steffi Goffart

Research output: Contribution to journalArticle

Abstract

To further understand pathways coordinating the expression of nuclear genes encoding mitochondrial proteins, we studied mitochondrial biogenesis during differentiation of myoblasts to myotubes. This energy-demanding process was accompanied by a fivefold increase of ATP turnover, covered by an eightfold increase of mitochondrial activity. While no change in mitochondrial DNA copy number was observed, mRNAs as well as proteins for nucleus-encoded cytochrome c, cytochrome c oxidase subunit IV, and mitochondrial transcription factor A (TFAM) increased, together with total cellular RNA and protein levels. Detailed analysis of the cytochrome c promoter by luciferase reporter, binding affinity, and electrophoretic mobility shift assays as well as mutagenesis studies revealed a critical role for cyclic AMP responsive element binding protein 1 (CREB-I) for promoter activation. Expression of two CREB-1 isoforms was observed by using specific antibodies and quantitative reverse transcription-PCR, and a shift from phosphorylated CREB-1Δ in myoblasts to phosphorylated CREB-1α protein in myotubes was shown, while mRNA ratios remained unchanged. Chromatin immunoprecipitation assays confirmed preferential binding of CREB-1α in situ to the cytochrome c promoter in myotubes. Overexpression of constitutively active and dominant-negative forms supported the key role of CREB-1 in regulating the expression of genes encoding mitochondrial proteins during myogenesis and probably also in other situations of enhanced mitochondrial biogenesis. Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Original languageEnglish
Pages (from-to)2446-2459
Number of pages14
JournalMolecular Cell Biology
Volume28
Issue number7
DOIs
Publication statusPublished - Apr 2008

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Skeletal Muscle Fibers
Organelle Biogenesis
Cytochromes c
Skeletal Muscle
Up-Regulation
Myoblasts
Mitochondrial Proteins
Gene Expression
Cyclic AMP Response Element-Binding Protein
Messenger RNA
Muscle Development
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Electron Transport Complex IV
Microbiology
Luciferases
Mitochondrial DNA
Mutagenesis
Cyclic AMP
Reverse Transcription

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Franko, Andras ; Mayer, Sabine ; Thiel, Gerald ; Mercy, Ludovic ; Arnould, Thierry ; Hornig-Do, Hue Tran ; Wiesner, Rudolf J. ; Goffart, Steffi. / CREB-1α is recruited to and mediates upregulation of the cytochrome c promoter during enhanced mitochondrial biogenesis accompanying skeletal muscle differentiation. In: Molecular Cell Biology. 2008 ; Vol. 28, No. 7. pp. 2446-2459.
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CREB-1α is recruited to and mediates upregulation of the cytochrome c promoter during enhanced mitochondrial biogenesis accompanying skeletal muscle differentiation. / Franko, Andras; Mayer, Sabine; Thiel, Gerald; Mercy, Ludovic; Arnould, Thierry; Hornig-Do, Hue Tran; Wiesner, Rudolf J.; Goffart, Steffi.

In: Molecular Cell Biology, Vol. 28, No. 7, 04.2008, p. 2446-2459.

Research output: Contribution to journalArticle

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AU - Franko, Andras

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