骨骼肌
生物
心肌细胞
线粒体
细胞生物学
基因表达
干细胞
下调和上调
基因表达调控
小RNA
细胞分化
氧化磷酸化
基因
内分泌学
遗传学
生物化学
作者
Stas Wüst,Stefan Dröse,Juliana Heidler,Ilka Wittig,Ina Klockner,András Frankó,Erik Bonke,Stefan Günther,Ulrich Gärtner,Thomas Boettger,Thomas Braun
出处
期刊:Cell Metabolism
[Elsevier]
日期:2018-05-01
卷期号:27 (5): 1026-1039.e6
被引量:82
标识
DOI:10.1016/j.cmet.2018.02.022
摘要
Muscle stem cells undergo a dramatic metabolic switch to oxidative phosphorylation during differentiation, which is achieved by massively increased mitochondrial activity. Since expression of the muscle-specific miR-1/133a gene cluster correlates with increased mitochondrial activity during muscle stem cell (MuSC) differentiation, we examined the potential role of miR-1/133a in metabolic maturation of skeletal muscles in mice. We found that miR-1/133a downregulate Mef2A in differentiated myocytes, thereby suppressing the Dlk1-Dio3 gene cluster, which encodes multiple microRNAs inhibiting expression of mitochondrial genes. Loss of miR-1/133a in skeletal muscles or increased Mef2A expression causes continuous high-level expression of the Dlk1-Dio3 gene cluster, compromising mitochondrial function. Failure to terminate the stem cell-like metabolic program characterized by high-level Dlk1-Dio3 gene cluster expression initiates profound changes in muscle physiology, essentially abrogating endurance running. Our results suggest a major role of miR-1/133a in metabolic maturation of skeletal muscles but exclude major functions in muscle development and MuSC maintenance.
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