Regulation of Mitoflash Biogenesis and Signaling by Mitochondrial Dynamics.

Regulation of Mitoflash Biogenesis and Signaling by Mitochondrial Dynamics.
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线粒体动力学对线粒体生物发生和信号传导的调节

DOI:
10.1038/srep32933
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发表时间:
2016-09-13
期刊:
影响因子:
4.6
通讯作者:
Cheng H
Cheng H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li W;Sun T;Liu B;Wu D;Qi W;Wang X;Ma Q;Cheng H

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线粒体是高度动态的细胞器,经历不断的网络重组,并以线粒体闪光(mitoflash)的形式表现出随机信号事件。在这里,我们研究线粒体网络动力学是否以及如何调节线粒体闪速的生物发生和信号传导。我们发现,在没有丝裂酶(Mfn) 1、Mfn2或Kif5b的情况下,当网络片段化或重新分布时,丝裂闪频率基本不变。然而,由于呼吸功能的叠加变化,Opa1缺乏降低了自发丝裂闪的频率,而尽管网络分裂,丝裂闪对非代谢刺激的反应没有变化。在线粒体过度灌注到单个全细胞网的Drp1或mff缺陷细胞中,规则振幅和持续时间的有丝分裂的频率再次保持不变,尽管由于检测能力的提高,出现了短暂和低振幅的“微闪烁”。然而,随着网络的重组,mitoflash信号的信号质量会根据网络的连通性进行动态调节。这些发现证明了线粒体网络动力学的新功能作用,并揭示了线粒体闪光信号调节的幅度而不是频率调节机制。此外,我们的数据支持一个随机触发模型的点火丝裂闪。
Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation. In Drp1- or Mff-deficient cells whose mitochondria hyperfused into a single whole-cell reticulum, the frequency of mitoflashes of regular amplitude and duration was again unaltered, although brief and low-amplitude “miniflashes” emerged because of improved detection ability. As the network reorganized, however, the signal mass of mitoflash signaling was dynamically regulated in accordance with the degree of network connectivity. These findings demonstrate a novel functional role of mitochondrial network dynamics and uncover a magnitude- rather than frequency-modulatory mechanism in the regulation of mitoflash signaling. In addition, our data support a stochastic trigger model for the ignition of mitoflashes.
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