The role of the mechanistic target of rapamycin complex 1 in the regulation of mitochondrial adaptation during skeletal muscle atrophy under denervation or calorie restriction in mice.

IF 2.4 4区 医学 Q3 NUTRITION & DIETETICS
Kazuki Uemichi, Takanaga Shirai, Ryunosuke Matsuno, Tomohiro Iwata, Riku Tanimura, Tohru Takemasa
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引用次数: 0

Abstract

Mechanistic target of rapamycin complex 1 (mTORC1) is a protein complex that regulates skeletal muscle protein synthesis and hypertrophy. mTORC1-mediated signaling activities are activated during denervation-induced skeletal muscle atrophy and suppressed during calorie restriction-induced atrophy. Mitochondria control the qualitative plasticity of skeletal muscles primarily through biogenesis, fusion, and fission. We recently showed that mTORC1 activation contributes toward mitochondrial homeostasis. In this study, we examined the role of mTORC1 in mitochondrial adaptation during denervation- or calorie restriction-induced skeletal muscle atrophy. Seven-week-old Institute of Cancer Research mice were subjected to 14 days of denervation or calorie restriction combined with the administration of the mTORC1 inhibitor-"rapamycin". Our results showed that although mTORC1 inhibition did not alter mitochondrial biogenesis, content and enzyme activity, it suppressed the activation of dynamin-related protein 1 (DRP1), a mitochondrial fission-related protein in denervated muscle, and reduced DRP1 expression in calorie-restricted muscle. Furthermore, calorie restriction-induced mitochondrial fragmentation was partially suppressed by mTORC1 inhibition. Taken together, our results indicate that mTORC1 activation upon denervation and inhibition upon calorie restriction contributes to qualitative changes in muscle plasticity by at least partially regulating the mitochondrial fission response.

雷帕霉素复合物1的机制靶点在小鼠去神经支配或热量限制下骨骼肌萎缩期间线粒体适应调节中的作用。
雷帕霉素复合体1 (Mechanistic target of rapamycin complex 1, mTORC1)是一种调节骨骼肌蛋白合成和肥厚的蛋白复合体。mtorc1介导的信号活动在去神经支配诱导的骨骼肌萎缩期间被激活,在卡路里限制诱导的萎缩期间被抑制。线粒体主要通过生物发生、融合和裂变来控制骨骼肌的定性可塑性。我们最近发现mTORC1激活有助于线粒体稳态。在这项研究中,我们研究了mTORC1在去神经支配或卡路里限制引起的骨骼肌萎缩期间线粒体适应中的作用。7周大的癌症研究所小鼠接受了14天的去神经或热量限制,同时给予mTORC1抑制剂“雷帕霉素”。我们的研究结果表明,尽管mTORC1抑制不会改变线粒体的生物发生、含量和酶活性,但它抑制了去神经支配肌肉中线粒体分裂相关蛋白DRP1的激活,并降低了DRP1在热量限制肌肉中的表达。此外,热量限制诱导的线粒体断裂被mTORC1抑制部分抑制。综上所述,我们的研究结果表明,mTORC1在去神经支配时的激活和卡路里限制时的抑制,至少部分地调节了线粒体裂变反应,从而有助于肌肉可塑性的质变。
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来源期刊
CiteScore
6.50
自引率
2.90%
发文量
113
审稿时长
4-8 weeks
期刊介绍: Applied Physiology, Nutrition, and Metabolism publishes original research articles, reviews, and commentaries, focussing on the application of physiology, nutrition, and metabolism to the study of human health, physical activity, and fitness. The published research, reviews, and symposia will be of interest to exercise physiologists, physical fitness and exercise rehabilitation specialists, public health and health care professionals, as well as basic and applied physiologists, nutritionists, and biochemists.
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