Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation.
Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation.
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DOI：
10.1038/cdd.2010.48
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发表时间：
2010-11
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在成肌分化过程中，成肌细胞的短线粒体转变为肌管中观察到的广泛延长的网络。其功能相关性和驱动线粒体网络形成的分子机制尚不清楚。我们现在表明，线粒体伸长是发生肌肉形成所必需的，这一事件取决于一氧化氮（NO）的细胞生成。抑制NO合成肌原性前体细胞导致线粒体延伸和肌原性分化的抑制。这是由于促裂变GTPase动力蛋白相关蛋白-1 （Drp1）与线粒体的活性增强、易位和对接，导致潜在的线粒体功能障碍，增加了对凋亡刺激的敏感性。在含有Drp1显性阴性形式的肌原性前体细胞中未观察到这些NO抑制作用。可溶性鸟苷酸环化酶介导了no依赖性Drp1作用的抑制和线粒体完整性和功能的维持。这些数据揭示了将线粒体形态和功能与肌源性分化联系起来的分化调节的新水平。
During myogenic differentiation the short mitochondria of myoblasts change into the extensively elongated network observed in myotubes. The functional relevance and the molecular mechanisms driving the formation of this mitochondrial network are unknown. We now show that mitochondrial elongation is required for myogenesis to occur and that this event depends on the cellular generation of nitric oxide (NO). Inhibition of NO synthesis in myogenic precursor cells leads to inhibition of mitochondrial elongation and of myogenic differentiation. This is due to the enhanced activity, translocation and docking of the pro-fission GTPase dynamin-related protein-1 (Drp1) to mitochondria, leading also to a latent mitochondrial dysfunction that increased sensitivity to apoptotic stimuli. These effects of NO inhibition were not observed in myogenic precursor cells containing a dominant-negative form of Drp1. Both NO-dependent repression of Drp1 action and maintenance of mitochondrial integrity and function were mediated through the soluble guanylate cyclase. These data uncover a novel level of regulation of differentiation linking mitochondrial morphology and function to myogenic differentiation.
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影响因子：
11.4
作者：
Barsoum, Mark J.;Yuan, Hua;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella
影响因子：
11.4
作者：
Collins, TJ;Berridge, MJ;Bootman, MD
通讯作者：
Bootman, MD
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
4.8
作者：
Bulotta, S;Barsacchi, R;Clementi, E
通讯作者：
Clementi, E
DOI：
10.1073/pnas.0610270104
发表时间：
2007-01-16
影响因子：
11.1
作者：
Angelin, Alessia;Tiepolo, Tania;Bernardi, Paolo
通讯作者：
Bernardi, Paolo