Dendritic mitochondria reach stable positions during circuit development.
Dendritic mitochondria reach stable positions during circuit development.
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DOI：
10.7554/elife.11583
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发表时间：
2016-01-07
期刊：
影响因子：
7.7
通讯作者：
Kerschensteiner D
中科院分区：
文献类型：
--
作者：
Faits MC;Zhang C;Soto F;Kerschensteiner D
线粒体在神经元树突中移动并定位于能量需求的位点。树突状线粒体作为高度能动的细胞器，其分布不断调整神经元活动通过钙依赖性逮捕的流行观点是基于在培养的神经元暴露于人工刺激的观察。在这里，我们分析了线粒体在完整的视网膜神经节细胞树突的运动。我们发现，在发育过程中，30%的线粒体在任何时候都是能动的，而随着树突的成熟，线粒体几乎停止移动并稳定地定位于突触和分支点。无论是自发的，也不是感觉诱发的活动和Ca2+瞬变改变树突状线粒体的运动性和视网膜变性的小鼠模型中的病理性活动过度升高，而不是降低运动性。因此，我们的研究结果表明，树突状线粒体达到稳定的位置在一个关键的发展时期的高运动性，并挑战目前的观点活动在调节树突线粒体运输的作用。http://dx.doi.org/10.7554/eLife.11583.001在动物和植物的细胞内，被称为线粒体的隔间起着几个重要的作用，包括为细胞过程提供化学能量。神经细胞内的线粒体在每个细胞的主体中产生，并且必须沿着称为轴突的长神经纤维和称为树突的分支状延伸部行进，以到达最需要它们的部位。随着神经细胞的形成，树突状分支随着不同神经细胞之间的连接（称为突触）的形成和消失而生长和收缩。后来，树突和突触变得更加稳定，但不清楚线粒体移动的数量是否也发生了变化。Faits等人使用显微镜研究了小鼠眼中神经节细胞树突发育中线粒体的运动。实验表明，在神经细胞发育的早期，线粒体是非常移动的。然而，随着突触变得更加稳定，线粒体变得几乎静止不动。另一种类型的细胞隔室向树突的运动不受影响，这表明这种运动的下降是线粒体特有的。接下来，Faits等人研究了患有视网膜退化的突变小鼠。这些小鼠的神经节细胞显示出比正常水平更高的自发活动，它们的突触在发育后期继续形成和消失。实验表明，成年突变小鼠神经节细胞中的线粒体保持移动的。Faits等人“的发现挑战了树突中线粒体的流行观点，并表明线粒体在视网膜发育的关键时期达到稳定的位置。进一步的研究应该揭示线粒体运动的下降是如何调节的，这可能有助于我们理解线粒体运动的差异如何导致某些人类疾病中神经细胞的变性，例如显性视神经萎缩。DOI：http://dx.doi.org/10.7554/eLife.11583.002网站
Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites. DOI: http://dx.doi.org/10.7554/eLife.11583.001 Inside the cells of animals and plants, compartments called mitochondria play several important roles including supplying chemical energy for cellular processes. The mitochondria inside nerve cells are produced in the main body of each cell, and must travel down a long nerve fiber called the axon and the branch-like extensions called dendrites to reach the sites where they are most needed. As the nerve cells form, dendritic branches grow and retract as the connections between different nerve cells – known as synapses – form and disappear. Later on, the dendrites and synapses become more stable, but it is not clear if the amount that the mitochondria move also changes. Faits et al. used microscopy to study the movement of mitochondria in the developing dendrites of ganglion cells in the eyes of mice. The experiments show that early on in the development of nerve cells, the mitochondria are very mobile. However, as the synapses become more stable later on, the mitochondria become almost motionless. The movement of another type of cell compartment to the dendrites is unaffected, which suggests that this decline in movement is specific to mitochondria. Next, Faits et al. studied mutant mice that suffer from degeneration of part of the eye called the retina. These mice have ganglion cells that display higher levels of spontaneous activity than normal and their synapses continue to form and disappear later in development. The experiments show that the mitochondria in the ganglion cells remain mobile in the adult mutant mice. Faits et al.’s findings challenge the prevailing views of mitochondria in dendrites, and suggest that mitochondria reach stable positions during a critical period in the development of the retina. Further studies should reveal how the decline in the movement of mitochondria is regulated, which may help us to understand how differences in the movement of mitochondria can lead to the degeneration of nerve cells in some human diseases, such as dominant optic atrophy. DOI: http://dx.doi.org/10.7554/eLife.11583.002