Zmynd17 controls muscle mitochondrial quality and whole-body metabolism
Zmynd17 controls muscle mitochondrial quality and whole-body metabolism
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DOI：
10.1096/fj.201701264r
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发表时间：
2018-09-01
期刊：
影响因子：
4.8
通讯作者：
Ono, Yusuke
中科院分区：
文献类型：
--
作者：
Fujita, Ryo;Yoshioka, Kiyoshi;Ono, Yusuke
肌肉线粒体对全身代谢功能至关重要，但它们的调节仍不清楚。锌指MYND结构域蛋白17（Zmynd17）是最近发现的哺乳动物肌肉特异性基因。在这里，我们研究了Zmynd17在小鼠中的作用。我们发现Zmynd17主要在骨骼肌中表达，尤其是在快速糖酵解的肌肉中。基因Zmynd17失活导致肌肉线粒体的形态和功能异常，导致呼吸功能下降。高脂饮食诱导的代谢应激上调了Zmynd17的表达，并进一步加剧了Zmynd17缺陷小鼠的肌肉线粒体形态。引人注目的是，Zmynd17缺乏显著加重了代谢应激诱导的肝脂肪变性、葡萄糖耐受不良和胰岛素抵抗。此外，缺乏Zmynd17的中年小鼠表现出有氧运动能力受损，葡萄糖耐受不良和胰岛素抵抗。因此，我们的研究结果表明，Zmynd17是一种代谢应激诱导因子，可维持肌肉线粒体的完整性，其缺乏会深刻影响全身葡萄糖代谢。Yoshioka，K.，Seko，D.，Suematsu，T.，Mitsuhashi，S.，Senoo，N.，Miura，S.，西野岛Ono，Y. Zmynd17控制肌肉线粒体质量和全身代谢。
Muscle mitochondria are crucial for systemic metabolic function, yet their regulation remains unclear. The zinc finger MYND domain-containing protein 17 (Zmynd17) was recently identified as a muscle-specific gene in mammals. Here, we investigated the role of Zmynd17 in mice. We found Zmynd17 predominantly expressed in skeletal muscle, especially in fast glycolytic muscle. Genetic Zmynd17 inactivation led to morphologic and functional abnormalities in muscle mitochondria, resulting in decreased respiratory function. Metabolic stress induced by a high-fat diet upregulated Zmynd17 expression and further exacerbated muscle mitochondrial morphology in Zmynd17-deficient mice. Strikingly, Zmynd17 deficiency significantly aggravated metabolic stress-induced hepatic steatosis, glucose intolerance, and insulin resistance. Furthermore, middle-aged mice lacking Zmynd17 exhibited impaired aerobic exercise performance, glucose intolerance, and insulin resistance. Thus, our results indicate that Zmynd17 is a metabolic stress-inducible factor that maintains muscle mitochondrial integrity, with its deficiency profoundly affecting whole-body glucose metabolism.Fujita, R., Yoshioka, K., Seko, D., Suematsu, T., Mitsuhashi, S., Senoo, N., Miura, S., Nishino, I., Ono, Y. Zmynd17 controls muscle mitochondrial quality and whole-body metabolism.