Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity
Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity
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DOI：
10.1096/fj.11-195933
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发表时间：
2012-02-01
期刊：
影响因子：
4.8
通讯作者：
Casas, Francois
中科院分区：
文献类型：
--
作者：
Pessemesse, Laurence;Schlernitzauer, Audrey;Casas, Francois
在脊椎动物中，骨骼肌肌纤维显示出与不同的线粒体含量和活性相关的收缩和代谢特性。我们先前已经鉴定出调节线粒体转录和线粒体生物发生的线粒体三一个肌酸受体（p43）。当骨骼肌过表达时，它会增加线粒体DNA含量，刺激线粒体呼吸，并诱导肌肉纤维的代谢和收缩特征的转移，向较慢，更氧化的表型。在这里，我们表明，小鼠的P43耗竭降低了骨骼肌中的线粒体DNA复制和呼吸链活性，并诱导了糖酵解肌肉表型更高，毛细血管密度降低。此外，相对于对照动物，P43（ - / - ）小鼠的肌肉质量显着增加，并且使用脂质的能力提高了。我们的发现表明，p43线粒体受体强烈影响肌纤维的肌肉质量以及代谢和收缩的特征，并提供了证据，证明该受体介导甲状腺激素在骨骼肌中的影响。 ，Sar，C.，Levin，J.，Grandemange，S.，Seyer，P.，Favier，F。 B.，Kaminski，S.，Cabello，G.，Wrutniak-Cabello，C.，Casas，F。小鼠中P43线粒体T3受体的耗竭会影响骨骼肌的发育和活动。 Faseb J. 26，748-756（2012）。 www.fasebj.org
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.-Pessemesse, L., Schlernitzauer, A., Sar, C., Levin, J., Grandemange, S., Seyer, P., Favier, F. B., Kaminski, S., Cabello, G., Wrutniak-Cabello, C., Casas, F. Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity. FASEB J. 26, 748-756 (2012). www.fasebj.org