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

Laurence Pessemesse (1) , Audrey Schlernitzauer , Chamroeun Sar (2) , Jonathan Levin (1) , Stéphanie Grandemange (3) , Pascal Seyer (4) , François Bertrand Favier , Sandra Kaminski (5) , Gérard Cabello , Chantal Wrutniak Cabello (1) , François Casas (1)

1 DMEM - Dynamique Musculaire et Métabolisme
2 INM - Institut des Neurosciences de Montpellier
3 SIGRETO - Signalisation, Génomique et Recherche Translationnelle en Oncologie
4 IGF - Institut de Génomique Fonctionnelle
5 IGMM - Institut de Génétique Moléculaire de Montpellier

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.

Mots clés: metabolism; thyroid hormone

Domaines: Biologie animale

Laurence Pessemesse, Audrey Schlernitzauer, Chamroeun Sar, Jonathan Levin, Stéphanie Grandemange, et al.. Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity.. FASEB Journal, 2012, 26 (2), pp.748-756. ⟨10.1096/fj.11-195933⟩. ⟨hal-00746541⟩