Novel Role of Tieg1 in Muscle Metabolism and Mitochondrial Oxidative Capacities

Autor: Malayannan Subramaniam, Maud Beuvin, Elizabeth S. Bruinsma, Lydie Nadal-Desbarats, Gisèle Bonne, Sabine F. Bensamoun, Steven A. Johnsen, Molly Nelson Holte, Philippe Pouletaut, William Même, Vladimir Veksler, Malek Kammoun, John R. Hawse, Jérôme Piquereau, Sandra Même, Yann Le Fur, Jean-Marc Constans, Zeynab Najafova, Frédéric Szeremeta
Přispěvatelé: Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Department of Biochemistry and Molecular Biology, Mayo Clinic, Department of General, Visceral, Vascular and Pediatric Surgery, Saarland University [Saarbrücken], Labex MS2TNIH (R01 DE14036 )Eisenberg Foundation, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pouletaut, Philippe, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Skeletal Muscle
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Physiology
Oxidative phosphorylation
030204 cardiovascular system & hematology
Mitochondrion
Tieg1
Electron Transport Complex IV
Mice
03 medical and health sciences
0302 clinical medicine
Physical Conditioning
Animal
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
medicine
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Animals
Citrate synthase
Cytochrome c oxidase
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Sarcomere organization
Muscle
Skeletal
Mice
Knockout
Soleus muscle
biology
Chemistry
Muscles
[SDV.BA]Life Sciences [q-bio]/Animal biology
Respiratory chain complex
Skeletal muscle
musculoskeletal system
Cell biology
Mitochondria
DNA-Binding Proteins
Succinate Dehydrogenase
Disease Models
Animal
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Metabolism
Metabolome
biology.protein
Female
Klf10
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
[PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis
Statistics and Probability [physics.data-an]
Transcription Factors
Zdroj: Acta Physiologica
Acta Physiologica, 2020, 228 (3), pp.e13394. ⟨10.1111/apha.13394⟩
Acta Physiologica, Wiley, 2020, 228 (3), pp.e13394. ⟨10.1111/apha.13394⟩
ISSN: 1748-1708
1748-1716
Popis: International audience; 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.
Databáze: OpenAIRE
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