Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities

Malek Kammoun, Jerome Piquereau, Lydie Nadal-Desbarats, Sandra Même, Maud Beuvin, Gisèle Bonne, Vladimir Veksler, Yann Le Fur, Philippe Pouletaut, William Même, Frederic Szeremeta, Jean Marc Constans, Elizabeth S. Bruinsma, Molly H. Nelson Holte, Zeynab Najafova, Steven A. Johnsen, Malayannan Subramaniam, John R. Hawse, Sabine F. Bensamoun

Research output: Contribution to journalArticle

Abstract

Aim: Tieg1 is involved in multiple signalling pathways, human diseases, and is highly expressed in muscle where its functions are poorly understood. Methods: We have utilized Tieg1 knockout (KO) mice to identify novel and important roles for this transcription factor in regulating muscle ultrastructure, metabolism and mitochondrial functions in the soleus and extensor digitorum longus (EDL) muscles. RNA sequencing, immunoblotting, transmission electron microscopy, MRI, NMR, histochemical and mitochondrial function assays were performed. Results: Loss of Tieg1 expression resulted in altered sarcomere organization and a significant decrease in mitochondrial number. Histochemical analyses demonstrated an absence of succinate dehydrogenase staining and a decrease in cytochrome c oxidase (COX) enzyme activity in KO soleus with similar, but diminished, effects in the EDL. Decreased complex I, COX and citrate synthase (CS) activities were detected in the soleus muscle of KO mice indicating altered mitochondrial function. Complex I activity was also diminished in KO EDL. Significant decreases in CS and respiratory chain complex activities were identified in KO soleus. 1H-NMR spectra revealed no significant metabolic difference between wild-type and KO muscles. However, 31P spectra revealed a significant decrease in phosphocreatine and ATPγ. Altered expression of 279 genes, many of which play roles in mitochondrial and muscle function, were identified in KO soleus muscle. Ultimately, all of these changes resulted in an exercise intolerance phenotype in Tieg1 KO mice. Conclusion: Our findings have implicated novel roles for Tieg1 in muscle including regulation of gene expression, metabolic activity and organization of tissue ultrastructure. This muscle phenotype resembles diseases associated with exercise intolerance and myopathies of unknown consequence.

Original languageEnglish (US)
Article numbere13394
JournalActa Physiologica
DOIs
StateAccepted/In press - Jan 1 2019

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Muscles
Knockout Mice
Citrate (si)-Synthase
Skeletal Muscle
RNA Sequence Analysis
Phenotype
Sarcomeres
Succinate Dehydrogenase
Phosphocreatine
Gene Expression Regulation
Muscular Diseases
Electron Transport Complex IV
Electron Transport
Transmission Electron Microscopy
Immunoblotting
Oxidoreductases
Transcription Factors
Adenosine Triphosphate
Staining and Labeling
Gene Expression

Keywords

  • Klf10
  • metabolism
  • mitochondria
  • skeletal muscle
  • Tieg1

ASJC Scopus subject areas

  • Physiology

Cite this

Kammoun, M., Piquereau, J., Nadal-Desbarats, L., Même, S., Beuvin, M., Bonne, G., ... Bensamoun, S. F. (Accepted/In press). Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities. Acta Physiologica, [e13394]. https://doi.org/10.1111/apha.13394

Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities. / Kammoun, Malek; Piquereau, Jerome; Nadal-Desbarats, Lydie; Même, Sandra; Beuvin, Maud; Bonne, Gisèle; Veksler, Vladimir; Le Fur, Yann; Pouletaut, Philippe; Même, William; Szeremeta, Frederic; Constans, Jean Marc; Bruinsma, Elizabeth S.; Nelson Holte, Molly H.; Najafova, Zeynab; Johnsen, Steven A.; Subramaniam, Malayannan; Hawse, John R.; Bensamoun, Sabine F.

In: Acta Physiologica, 01.01.2019.

Research output: Contribution to journalArticle

Kammoun, M, Piquereau, J, Nadal-Desbarats, L, Même, S, Beuvin, M, Bonne, G, Veksler, V, Le Fur, Y, Pouletaut, P, Même, W, Szeremeta, F, Constans, JM, Bruinsma, ES, Nelson Holte, MH, Najafova, Z, Johnsen, SA, Subramaniam, M, Hawse, JR & Bensamoun, SF 2019, 'Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities', Acta Physiologica. https://doi.org/10.1111/apha.13394
Kammoun M, Piquereau J, Nadal-Desbarats L, Même S, Beuvin M, Bonne G et al. Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities. Acta Physiologica. 2019 Jan 1. e13394. https://doi.org/10.1111/apha.13394
Kammoun, Malek ; Piquereau, Jerome ; Nadal-Desbarats, Lydie ; Même, Sandra ; Beuvin, Maud ; Bonne, Gisèle ; Veksler, Vladimir ; Le Fur, Yann ; Pouletaut, Philippe ; Même, William ; Szeremeta, Frederic ; Constans, Jean Marc ; Bruinsma, Elizabeth S. ; Nelson Holte, Molly H. ; Najafova, Zeynab ; Johnsen, Steven A. ; Subramaniam, Malayannan ; Hawse, John R. ; Bensamoun, Sabine F. / Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities. In: Acta Physiologica. 2019.
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AU - Piquereau, Jerome

AU - Nadal-Desbarats, Lydie

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AU - Bonne, Gisèle

AU - Veksler, Vladimir

AU - Le Fur, Yann

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AU - Même, William

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AU - Constans, Jean Marc

AU - Bruinsma, Elizabeth S.

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AU - Najafova, Zeynab

AU - Johnsen, Steven A.

AU - Subramaniam, Malayannan

AU - Hawse, John R.

AU - Bensamoun, Sabine F.

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