Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites.
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites.
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DOI：
10.1016/j.celrep.2016.09.004
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发表时间：
2016-10-04
期刊：
影响因子：
8.8
通讯作者：
Kittler JT
中科院分区：
文献类型：
--
作者：
López-Doménech G;Higgs NF;Vaccaro V;Roš H;Arancibia-Cárcamo IL;MacAskill AF;Kittler JT
正确的线粒体分布对于满足局部能量需求和钙缓冲需求以及支持关键细胞过程至关重要。神经靶向蛋白Miro 1和Miro 2是线粒体转运机制的重要组成部分，但它们在神经元发育、维持和存活中的具体作用仍知之甚少。使用小鼠基因敲除策略，我们证明，Miro 1，而不是Miro 2，是轴突和树突的线粒体运输的主要调节。Miro 1缺失导致线粒体从远端树突，但不是轴突，伴随着树突的复杂性显着减少。通过删除成熟神经元中的Miro 1来破坏出生后线粒体在体内的分布，导致远端树突的进行性丧失并损害神经元的存活。因此，线粒体质量的局部可用性对于产生和维持树突状乔木是至关重要的，并且成熟神经元中线粒体分布的破坏与神经变性相关。Miro 1缺失改变树突中的线粒体分布，但不改变轴突线粒体分布影响树突发育正确的线粒体分布是维持复杂树突几何形状的关键异常树突线粒体分布引发神经变性复杂的树突形态对神经回路形成和大脑计算至关重要。López-Doménech等人证明Miro 1依赖的树突状线粒体定位关键调节树突树的发育和维持树枝化。破坏成熟神经元中的线粒体分布导致树突复杂性的丧失，这是神经变性的前兆。
Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration. Miro1 deletion alters mitochondrial distribution in dendrites but not axons Mitochondrial distribution impacts dendritic development Correct mitochondrial distribution is key to maintain complex dendritic geometries Aberrant dendritic mitochondrial distribution triggers neurodegeneration Complex dendritic morphologies are essential for neural circuit formation and brain computation. López-Doménech et al. demonstrate that Miro1-dependent dendritic mitochondrial positioning critically regulates the development of the dendritic tree and sustains arborization. Disrupting mitochondrial distribution in mature neurons leads to the loss of dendritic complexity, which precedes neurodegeneration.
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DOI：
10.1196/annals.1379.003
发表时间：
2007-01-01
期刊：
IMAGING AND THE AGING BRAIN
影响因子：
--
作者：
Grutzendler, Jaime;Helmin, Kathryn;Gan, Wen-Biao
通讯作者：
Gan, Wen-Biao
影响因子：
5.3
作者：
Eyal, Guy;Mansvelder, Huibert D.;Segev, Idan
通讯作者：
Segev, Idan
影响因子：
16.2
作者：
Horton, AC;Rácz, B;Ehlers, MD
通讯作者：
Ehlers, MD
影响因子：
64.5
作者：
NANGAKU, M;SATOYOSHITAKE, R;HIROKAWA, N
通讯作者：
HIROKAWA, N
影响因子：
21.3
作者：
Ishihara, Naotada;Nomura, Masatoshi;Mihara, Katsuyoshi
通讯作者：
Mihara, Katsuyoshi