Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity

• Published in: www.fasebj.org Vol. 2
• Main Authors: Pessemesse , Laurence (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Schlernitzauer , Audrey (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Sar , Chamroeun (Université Montpellier 1Institut National de la Santé et de la Recherche Médicale, MontpellierMontpellier(France).), Levin , Jonathan (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Grandemange , Marine (INRA , Champenoux (France). UMR 1092 Laboratoire d'Etudes des Ressources Forêt-Bois), Seyer , Pascal (Université Montpellier 1, Montpellier(France).), FAVIER , FRANCOIS (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Kaminski , Sandra (INRA Institut National de la Recherche Agronomique, Montpellier(France). UMR 0866 Dynamique Musculaire et Métabolisme ), Cabello , Gerard (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Chantal Wrutniak-Cabello , Chantal (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme ), Casas , Francois(auteur de correspondance) (INRA , Montpellier (France). UMR 0866 Dynamique Musculaire et Métabolisme )
• Format: Publication
• Language: English
• Published: 2012
• Subjects: metabolism; thyroid hormone

In vertebrates, skeletal muscle myofibers display different contractile and metabolic properties associated with different mitochondrial content and activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration, and induces a shift in the metabolic and contractile features of muscle fibers toward a slower and more oxidative phenotype. Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle in association with the induction of a more glycolytic muscle phenotype and a decrease of capillary density. In addition, p43(-/-) mice displayed a significant increase in muscle mass relative to control animals and had an improved ability to use lipids. Our findings establish that the p43 mitochondrial receptor strongly affects muscle mass and the metabolic and contractile features of myofibers and provides evidence that this receptor mediates, in part, the influence of thyroid hormone in skeletal muscle